nach oben

Current Sexual Health Reports

Erschienen in:

18.07.2019 | Preclinical and Psychophysiology (F Guarraci and L Marson, Section Editors)

Exploration of Ion Channels in the Clitoris: a Review

verfasst von: Gabrielle Moore, Zuri Ngozi, Crystal Burgess, Audrey Weber, Stacey Dutton

Erschienen in: Current Sexual Health Reports | Ausgabe 3/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose of the Review

This review investigates known research on ion channels expressed in the clitoris. Specifically, discussing the role these channels play in clitoral arousal, their contributions to sexual dysfunction, and their potential use as a pharmacological targeted treatment. In addition, we propose channels that should be considered as candidate proteins involved in female sexual dysfunction.

Recent Findings

Review of studies published from 1811–2017, found that only BK_Ca, SK, and TRPA1 channels have been explored in the clitoris. These studies have identified these channels in clitoral tissue and have suggested their involvement in the nitric oxide-cGMP mediated pathway of erection. However, these studies have not resulted in additional or improved treatment options for female patients with sexual dysfunction. Finally, we suggested the consideration of voltage-gated sodium channels as candidate proteins to explore in sexual dysfunction, due to the comorbid relationship with epilepsy.

Summary

Based on these findings, further research is needed into these channels and their role in female sexual arousal. Investments into this area of research have the potential for improving our understanding of sexual dysfunction of arousal, improving pharmacological treatments, and ultimately improving quality of life for patients.

Pauls RN. Anatomy of the clitoris and the female sexual response. Clin Anat. 2015;28(3):376–84. https://doi.org/10.1002/ca.22524.CrossRefPubMed

Baskin LS. Anatomical studies of the female genitalia: surgical reconstructive implications. J Pediatr Endocrinol Metab. 2004;17(4):581–7.CrossRefPubMed

O'Connell HE, Sanjeevan KV, Hutson JM. Anatomy of the clitoris. J Urol. 2005;174(4 Pt 1):1189–95.CrossRefPubMed

Yeung J, Pauls RN. Anatomy of the vulva and the female sexual response. Obstet Gynecol Clin N Am. 2016;43(1):27–44. https://doi.org/10.1016/j.ogc.2015.CrossRef

Pavone C, Giacalone N, Vella M, Urso L, Zummo L, Fierro B. Relation between sexual dysfunctions and epilepsy, type of epilepsy, type of antiepileptic drugs: a prospective study. Urologia. 2017;84(2):88–92. https://doi.org/10.5301/uro.5000222.CrossRefPubMed

American Psychiatric Association. DSM-5: Diagnostic and statistical manual for mental disorders. 5th ed. USA: American Psychiatric Press; 2013. https://doi.org/10.1176/appi.books.9780890425596.CrossRef

Martin-Alguacil N, Pfaff DW, Shelley DN, Schober JM. Clitoral sexual arousal: an immunocytochemical and innervation study of the clitoris. BJU Int. 2008;101(11):1407–13. https://doi.org/10.1111/j.1464-410X.2008.07625.x.CrossRefPubMed

Cibrian-Llanderal T, Tecamachaltzi-Silvaran M, Triana-Del Rio R, Pfaus JG, Manzo J, Coria-Avila GA. Clitoral stimulation modulates appetitive sexual behavior and facilitates reproduction in rats. Physiol Behav. 2010;100(2):148–53. https://doi.org/10.1016/j.physbeh.2010.02.015.CrossRefPubMed

Parada M, Chamas L, Censi S, Coria-Avila G, Pfaus JG. Clitoral stimulation induces conditioned place preference and Fos activation in the rat. Horm Behav. 2010;57(2):112–8. https://doi.org/10.1016/j.yhbeh.2009.05.008.CrossRefPubMed

10.

Parada M, Abdul-Ahad F, Censi S, Sparks L, Pfaus JG. Context alters the ability of clitoral stimulation to induce a sexually-conditioned partner preference in the rat. Horm Behav. 2011;59(4):520–7. https://doi.org/10.1016/j.yhbeh.2011.02.001.CrossRefPubMed

11.

Escayg A, Goldin AL. Sodium channel Scn1a and epilepsy: mutations and mechanisms. [Review]. Epilepsia. 2010;51:1650–8.CrossRefPubMedPubMedCentral

12.

Sutherland HG, Griffiths LR. Genetics of migraine: insights into the molecular basis of migraine disorders. Headache. 2017;57(4):537–69. https://doi.org/10.1111/head.13053.CrossRefPubMed

13.

Grimm C, Barthmes M, Wahl-Schott C. TRPML3. Handb Exp Pharmacol. 2014;222:659–74. https://doi.org/10.1007/978-3-642-54215-2_26.CrossRefPubMed

14.

Irie S, Furukawa T. TRPM1. Handb Exp Pharmacol. 2014;222:387–402. https://doi.org/10.1007/978-3-642-54215-2_15.CrossRefPubMed

15.

Jentsch TJ, Pusch M. CLC Chloride channels and transporters: structure, function, physiology, and disease. Physiol Rev. 2018;98(3):1493–590. https://doi.org/10.1152/physrev.00047.2017.CrossRefPubMed

16.

Huang B, Liu Y, Gao X, Xu J, Dai P, Zhu Q, et al. A novel pore-region mutation, c.887G > A (p.G296D) in KCNQ4, causing hearing loss in a Chinese family with autosomal dominant non-syndromic deafness 2. BMC Med Genet. 2017;18(1):36. https://doi.org/10.1186/s12881-017-0396-5.CrossRefPubMedPubMedCentral

17.

Poroca DR, Pelis RM, Chappe VM. ClC Channels and transporters: structure, physiological functions, and implications in human chloride channelopathies. Front Pharmacol. 2017;8:151. https://doi.org/10.3389/fphar.2017.00151.CrossRefPubMedPubMedCentral

18.

Shimomura K, Maejima Y. KATP Channel mutations and neonatal diabetes. Intern Med (Tokyo, Japan). 2017;56(18):2387–93. https://doi.org/10.2169/internalmedicine.8454-16.CrossRef

19.

Lambert M, Capuano V, Olschewski A, Sabourin J, Nagaraj C, Girerd B, et al. Ion channels in pulmonary hypertension: a therapeutic interest? Int J Mol Sci. 2018;19(10). https://doi.org/10.3390/ijms19103162.

20.

Valverde MA, Cantero-Recasens G, Garcia-Elias A, Jung C, Carreras-Sureda A, Vicente R. Ion channels in asthma. J Biol Chem. 2011;286(38):32877–82. https://doi.org/10.1074/jbc.R110.215491.CrossRefPubMedPubMedCentral

21.

Skinner JR, Winbo A, Abrams D, Vohra J, Wilde AA. Channelopathies that lead to sudden cardiac death: clinical and genetic aspects. Heart Lung Circ. 2019;28(1):22–30. https://doi.org/10.1016/j.hlc.2018.09.007.CrossRefPubMed

22.

Saito YA, Strege PR, Tester DJ, Locke GR 3rd, Talley NJ, Bernard CE, et al. Sodium channel mutation in irritable bowel syndrome: evidence for an ion channelopathy. Am J Physiol Gastrointest Liver Physiol. 2009;296(2):G211–8. https://doi.org/10.1152/ajpgi.90571.2008.CrossRefPubMed

23.

Pollak J, Rai KG, Funk CC, Arora S, Lee E, Zhu J, et al. Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy. PLoS One. 2017;12(3):e0172884. https://doi.org/10.1371/journal.pone.0172884.CrossRefPubMedPubMedCentral

24.

Aydin M, Bitkin A, Irkilata L, Yilmaz A, Moral C, Atilla MK. The effect of migraine and tension-type headaches on female sexual functions: a prospective, cross-sectional, controlled study. Turk J Urol. 2018;44(5):418–22. https://doi.org/10.5152/tud.2018.45228.CrossRefPubMedPubMedCentral

25.

Foy CG, Newman JC, Berlowitz DR, Russell LP, Kimmel PL, Wadley VG, et al. Blood pressure, sexual activity, and dysfunction in women with hypertension: baseline findings from the systolic blood pressure intervention trial (SPRINT). J Sex Med. 2016;13(9):1333–46. https://doi.org/10.1016/j.jsxm.2016.06.014.CrossRefPubMedPubMedCentral

26.

Maiorino MI, Bellastella G, Esposito K. Diabetes and sexual dysfunction: current perspectives. Diabetes Metab Syndr Obes. 2014;7:95–105. https://doi.org/10.2147/dmso.s36455.CrossRefPubMedPubMedCentral

27.

Matos G, Alvarenga TA, Tufik S, Andersen ML. Sexual dysfunction and epilepsy: the reasons beyond medications. Epilepsia. 2013;54(1):205–6. https://doi.org/10.1111/epi.12047.CrossRefPubMed

28.

Miner M, Kim ED. Cardiovascular disease and male sexual dysfunction. Asian J Androl. 2015;17(1):3–4.CrossRefPubMed

29.

Riviere P, Zallot C, Desobry P, Sabate JM, Vergniol J, Zerbib F, et al. Frequency of and factors associated with sexual dysfunction in patients with inflammatory bowel disease. J Crohns Colitis. 2017;11(11):1347–52. https://doi.org/10.1093/ecco-jcc/jjx100.CrossRefPubMed

30.

Soto Campos JG, Rojas Villegas J, Padilla Galo A, Marina Malanda N, Garcia Rivero JL, Pinedo Sierra C, et al. Impact of asthma on the sexual functioning of patients. a case-control study. Arch Bronconeumol. 2017;53(12):667–74. https://doi.org/10.1016/j.arbres.2017.05.011.CrossRefPubMed

31.

Tamas V, Kempler P. Sexual dysfunction in diabetes. Handb Clin Neurol. 2014;126:223–32. https://doi.org/10.1016/b978-0-444-53480-4.00017-5.CrossRefPubMed

32.

• Gragasin FS, Michelakis ED, Hogan A, Moudgil R, Hashimoto K, Wu X, et al. The neurovascular mechanism of clitoral erection: nitric oxide and cGMP-stimulated activation of BKCa channels. FASEB J. 2004;18(12):1382–91. https://doi.org/10.1096/fj.04-1978com This paper was the first to directly establish that clitorial erections worked through NO activation of BKCa channels. This is important because prior studies have implied this mechanism, but it was not tested. The results suggest a similar mechanism of erection for the clitoris and the penis . CrossRefPubMed

33.

Cellek S, Moncada S. Nitrergic neurotransmission mediates the non-adrenergic non-cholinergic responses in the clitoral corpus cavernosum of the rabbit. Br J Pharmacol. 1998;125(8):1627–9. https://doi.org/10.1038/sj.bjp.0702278.CrossRefPubMedPubMedCentral

34.

Ignarro LJ, Bush PA, Buga GM, Wood KS, Fukuto JM, Rajfer J. Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem Biophys Res Commun. 1990;170(2):843–50.CrossRefPubMed

35.

Kim YC, Davies MG, Hagen PO, Carson CC 3rd. Experimental evidence for endothelium dependent relaxation and neuronal nitric oxide in corpus cavernosum. Yonsei Med J. 1994;35(3):308–13. https://doi.org/10.3349/ymj.1994.35.3.308.CrossRefPubMed

36.

Spektor M, Rodriguez R, Rosenbaum RS, Wang HZ, Melman A, Christ GJ. Potassium channels and human corporeal smooth muscle cell tone: further evidence of the physiological relevance of the Maxi-K channel subtype to the regulation of human corporeal smooth muscle tone in vitro. J Urol. 2002;167(6):2628–35.CrossRefPubMed

37.

Kiraly I, Pataricza J, Bajory Z, Simonsen U, Varro A, Papp JG, et al. Involvement of large-conductance Ca(2+) -activated K(+) channels in both nitric oxide and endothelium-derived hyperpolarization-type relaxation in human penile small arteries. Basic Clin Pharmacol Toxicol. 2013;113(1):19–24. https://doi.org/10.1111/bcpt.12059.CrossRefPubMed

38.

Archer SL, Huang JM, Hampl V, Nelson DP, Shultz PJ, Weir EK. Nitric oxide and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cGMP-dependent protein kinase. Proc Natl Acad Sci U S A. 1994;91(16):7583–7. https://doi.org/10.1073/pnas.91.16.7583.CrossRefPubMedPubMedCentral

39.

Keravis T, Lugnier C. Cyclic nucleotide phosphodiesterase (PDE) isozymes as targets of the intracellular signalling network: benefits of PDE inhibitors in various diseases and perspectives for future therapeutic developments. Br J Pharmacol. 2012;165(5):1288–305. https://doi.org/10.1111/j.1476-5381.2011.01729.x.CrossRefPubMedPubMedCentral

40.

Verkauf BS, Von Thron J, O'Brien WF. Clitoral size in normal women. Obstet Gynecol. 1992;80(1):41–4.PubMed

41.

Park K, Moreland RB, Goldstein I, Atala A, Traish A. Sildenafil inhibits phosphodiesterase type 5 in human clitoral corpus cavernosum smooth muscle. Biochem Biophys Res Commun. 1998;249(3):612–7. https://doi.org/10.1006/bbrc.1998.9206.CrossRefPubMed

42.

Park JK, Kim JU, Lee SO, Hwang PH, Yi HK, Kim YG, et al. Nitric oxide-cyclic GMP signaling pathway in the regulation of rabbit clitoral cavernosum tone. Exp Biol Med (Maywood). 2002;227(11):1022–30.CrossRef

43.

Kun A, Matchkov VV, Stankevicius E, Nardi A, Hughes AD, Kirkeby HJ, et al. NS11021, a novel opener of large-conductance Ca(2+)-activated K(+) channels, enhances erectile responses in rats. Br J Pharmacol. 2009;158(6):1465–76. https://doi.org/10.1111/j.1476-5381.2009.00404.x.CrossRefPubMedPubMedCentral

44.

Gonzalez-Corrochano R, La Fuente J, Cuevas P, Fernandez A, Chen M. Saenz de Tejada I, et al. Ca2+ -activated K+ channel (KCa) stimulation improves relaxant capacity of PDE5 inhibitors in human penile arteries and recovers the reduced efficacy of PDE5 inhibition in diabetic erectile dysfunction. Br J Pharmacol. 2013;169(2):449–61. https://doi.org/10.1111/bph.12143.CrossRefPubMedPubMedCentral

45.

Sung HH, Kang SJ, Chae MR, Kim HK, Park JK, Kim CY, et al. Effect of BKCa Channel opener LDD175 on erectile function in an in vivo diabetic rat model. J Sex Med. 2017;14(1):59–68. https://doi.org/10.1016/j.jsxm.2016.11.316.CrossRefPubMed

46.

Gao L, Yang L, Qian S, Li T, Han P, Yuan J. Systematic review and meta-analysis of phosphodiesterase type 5 inhibitors for the treatment of female sexual dysfunction. Int J Gynaecol Obstet. 2016;133(2):139–45. https://doi.org/10.1016/j.ijgo.2015.08.015.CrossRefPubMed

47.

Perez-Lopez FR, Fernandez-Alonso AM, Trabalon-Pastor M, Vara C, Chedraui P. Assessment of sexual function and related factors in mid-aged sexually active Spanish women with the six-item Female Sex Function Index. Menopause (New York, NY). 2012;19(11):1224–30. https://doi.org/10.1097/gme.0b013e3182546242.CrossRef

48.

Verit FF, Verit A, Billurcu N. Low sexual function and its associated risk factors in pre- and postmenopausal women without clinically significant depression. Maturitas. 2009;64(1):38–42. https://doi.org/10.1016/j.maturitas.2009.07.002.CrossRefPubMed

49.

Jonusiene G, Zilaitiene B, Adomaitiene V, Aniuliene R, Bancroft J. Sexual function, mood and menopause symptoms in Lithuanian postmenopausal women. Climacteric. 2013;16(1):185–93. https://doi.org/10.3109/13697137.2012.682746.CrossRefPubMed

50.

Chedraui P, Perez-Lopez FR, Mezones-Holguin E, San Miguel G, Avila C. Assessing predictors of sexual function in mid-aged sexually active women. Maturitas. 2011;68(4):387–90. https://doi.org/10.1016/j.maturitas.2010.12.004.CrossRefPubMed

51.

Berman JR, Berman LA, Werbin TJ, Flaherty EE, Leahy NM, Goldstein I. Clinical evaluation of female sexual function: effects of age and estrogen status on subjective and physiologic sexual responses. Int J Impot Res. 1999;11(Suppl 1):S31–8.CrossRefPubMed

52.

Puppo V. Anatomy and physiology of the clitoris, vestibular bulbs, and labia minora with a review of the female orgasm and the prevention of female sexual dysfunction. Clin Anat. 2013;26(1):134–52. https://doi.org/10.1002/ca.22177.CrossRefPubMed

53.

Sah P, Faber ES. Channels underlying neuronal calcium-activated potassium currents. Prog Neurobiol. 2002;66(5):345–53.CrossRefPubMed

54.

Kohler M, Hirschberg B, Bond CT, Kinzie JM, Marrion NV, Maylie J, et al. Small-conductance, calcium-activated potassium channels from mammalian brain. Science. 1996;273(5282):1709–14.CrossRefPubMed

55.

Xia XM, Fakler B, Rivard A, Wayman G, Johnson-Pais T, Keen JE, et al. Mechanism of calcium gating in small-conductance calcium-activated potassium channels. Nature. 1998;395(6701):503–7. https://doi.org/10.1038/26758.CrossRefPubMed

56.

•• Chen MX, Gorman SA, Benson B, Singh K, Hieble JP, Michel MC, et al. Small and intermediate conductance Ca(2+)-activated K+ channels confer distinctive patterns of distribution in human tissues and differential cellular localisation in the colon and corpus cavernosum. Naunyn Schmiedeberg's Arch Pharmacol. 2004;369(6):602–15. https://doi.org/10.1007/s00210-004-0934-5 This is an important paper as it identified the presence of these channels in clitoral tissue and at higher levels compared with the penis. This is of significance due to SK channels role in the NO pathway and past observations of higher levels in male smooth muscle tissue that had undergone sex change procedures. CrossRef

57.

Tang YR, Yang WW, Wang Y, Gong YY, Jiang LQ, Lin L. Estrogen regulates the expression of small-conductance Ca-activated K+ channels in colonic smooth muscle cells. Digestion. 2015;91(3):187–96. https://doi.org/10.1159/000371544.CrossRefPubMed

58.

Matschke LA, Rinne S, Snutch TP, Oertel WH, Dolga AM, Decher N. Calcium-activated SK potassium channels are key modulators of the pacemaker frequency in locus coeruleus neurons. Mol Cell Neurosci. 2018;88:330–41. https://doi.org/10.1016/j.mcn.2018.03.002.CrossRefPubMed

59.

Ferreira-Neto HC, Biancardi VC, Stern JE. A reduction in SK channels contributes to increased activity of hypothalamic magnocellular neurons during heart failure. J Physiol. 2017;595(20):6429–42. https://doi.org/10.1113/jp274730.CrossRefPubMedPubMedCentral

60.

Mourre C, Manrique C, Camon J, Aidi-Knani S, Deltheil T, Turle-Lorenzo N, et al. Changes in SK channel expression in the basal ganglia after partial nigrostriatal dopamine lesions in rats: Functional consequences. Neuropharmacology. 2017;113(Pt A):519–32. https://doi.org/10.1016/j.neuropharm.2016.11.003.CrossRefPubMed

61.

Ballesteros-Merino C, Watanabe M, Shigemoto R, Fukazawa Y, Adelman JP, Lujan R. Differential subcellular localization of SK3-containing channels in the hippocampus. Eur J Neurosci. 2014;39(6):883–92. https://doi.org/10.1111/ejn.12474.CrossRefPubMed

62.

de Oliveira RM, Martin S, de Oliveira CL, Milani H, Schiavon AP, Joca S, et al. Eag1, Eag2, and SK3 potassium channel expression in the rat hippocampus after global transient brain ischemia. J Neurosci Res. 2012;90(3):632–40. https://doi.org/10.1002/jnr.22772.CrossRefPubMed

63.

Terstappen GC, Pellacani A, Aldegheri L, Graziani F, Carignani C, Pula G, et al. The antidepressant fluoxetine blocks the human small conductance calcium-activated potassium channels SK1, SK2 and SK3. Neurosci Lett. 2003;346(1, 2):85–8.CrossRefPubMed

64.

Abbasinazari M, Heidari-Kord M, Mazaheri-Meybodi A, Eshraghi A, Bayati N. Plasma oxytocin level and sexual dysfunction in depressed women treated by either fluoxetine or citalopram: a pilot clinical trial. Iran J Pharm Res. 2018;17(1):408–14.PubMedPubMedCentral

65.

Khazaie H, Rezaie L, Rezaei Payam N, Najafi F. Antidepressant-induced sexual dysfunction during treatment with fluoxetine, sertraline and trazodone; a randomized controlled trial. Gen Hosp Psychiatry. 2015;37(1):40–5. https://doi.org/10.1016/j.genhosppsych.2014.10.010.CrossRefPubMed

66.

Sorensen US, Strobaek D, Christophersen P, Hougaard C, Jensen ML, Nielsen EO, et al. Synthesis and structure-activity relationship studies of 2-(N-substituted)-aminobenzimidazoles as potent negative gating modulators ofsmall conductance Ca2+-activated K+ channels. J Med Chem. 2008;51(23):7625–34. https://doi.org/10.1021/jm800809f.CrossRefPubMed

67.

Nolting A, Ferraro T, D'Hoedt D, Stocker M. An amino acid outside the pore region influences apamin sensitivity in small conductance Ca2+-activated K+ channels. J Biol Chem. 2007;282(6):3478–86. https://doi.org/10.1074/jbc.M607213200.CrossRefPubMed

68.

•• Uckert S, Albrecht K, Bannowsky A, Sohn M, Kuczyk MA, Hedlund P. Expression and distribution of the transient receptor potential cationic channel A1 (TRPA1) in the human clitoris-comparison to male penile erectile tissue. Int J Impot Res. 2017;29(5):179–83. https://doi.org/10.1038/ijir.2017.15 This paper was the first to identify the presence of TRPA1 in clitoris tissue. This is important as it was the first mechano- sensor/pain channel characterized in the tissue. CrossRefPubMed

69.

Uckert S, Sonnenberg JE, Albrecht K, Kuczyk MA, Hedlund P. Expression and distribution of the transient receptor potential cationic channel ankyrin 1 (TRPA1) in the human vagina. Int J Impot Res. 2015;27(1):16–9. https://doi.org/10.1038/ijir.2014.23.CrossRefPubMed

70.

Jaquemar D, Schenker T, Trueb B. An ankyrin-like protein with transmembrane domains is specifically lost after oncogenic transformation of human fibroblasts. J Biol Chem. 1999;274(11):7325–33. https://doi.org/10.1074/jbc.274.11.7325.CrossRefPubMed

71.

Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Hricik TR, et al. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell. 2003;112(6):819–29.CrossRefPubMed

72.

Kwan KY, Allchorne AJ, Vollrath MA, Christensen AP, Zhang DS, Woolf CJ, et al. TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron. 2006;50(2):277–89. https://doi.org/10.1016/j.neuron.2006.03.042.CrossRefPubMed

73.

Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, et al. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron. 2004;41(6):849–57.CrossRefPubMed

74.

Bautista DM, Jordt SE, Nikai T, Tsuruda PR, Read AJ, Poblete J, et al. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell. 2006;124(6):1269–82. https://doi.org/10.1016/j.cell.2006.02.023.CrossRefPubMed

75.

Nilius B, Appendino G, Owsianik G. The transient receptor potential channel TRPA1: from gene to pathophysiology. Arch Eur J Physiol. 2012;464(5):425–58. https://doi.org/10.1007/s00424-012-1158-z.CrossRef

76.

Streng T, Axelsson HE, Hedlund P, Andersson DA, Jordt SE, Bevan S, et al. Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder. Eur Urol. 2008;53(2):391–9. https://doi.org/10.1016/j.eururo.2007.10.024.CrossRefPubMed

77.

Di A, Malik AB. TRP channels and the control of vascular function. Curr Opin Pharmacol. 2010;10(2):127–32. https://doi.org/10.1016/j.coph.2009.11.010.CrossRefPubMed

78.

Catterall WA. From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron. 2000;26(1):13–25.CrossRefPubMed

79.

Yu FH, Catterall WA. Overview of the voltage-gated sodium channel family. Genome Biol. 2003;4(3):207.CrossRefPubMedPubMedCentral

80.

Goldin AL, Barchi RL, Caldwell JH, Hofmann F, Howe JR, Hunter JC, et al. Nomenclature of voltage-gated sodium channels. Neuron. 2000;28(2):365–8.CrossRefPubMed

81.

Bosmans F, Martin-Eauclaire MF, Tytgat J. Differential effects of five 'classical' scorpion beta-toxins on rNav1.2a and DmNav1 provide clues on species-selectivity. Toxicol Appl Pharmacol. 2007;218(1):45–51. https://doi.org/10.1016/j.taap.2006.10.009.CrossRefPubMed

82.

Depienne C, Trouillard O, Saint-Martin C, Gourfinkel-An I, Bouteiller D, Carpentier W, et al. Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients. J Med Genet. 2009;46(3):183–91. https://doi.org/10.1136/jmg.2008.062323.CrossRefPubMed

83.

Kwan P, Poon WS, Ng HK, Kang DE, Wong V, Ng PW, et al. Multidrug resistance in epilepsy and polymorphisms in the voltage-gated sodium channel genes SCN1A, SCN2A, and SCN3A: correlation among phenotype, genotype, and mRNA expression. Pharmacogenet Genomics. 2008;18(11):989–98. https://doi.org/10.1097/FPC.0b013e3283117d67.CrossRefPubMed

84.

Mantegazza M, Curia G, Biagini G, Ragsdale DS, Avoli M. Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders. Lancet Neurol. 2010;9(4):413–24. https://doi.org/10.1016/s1474-4422(10)70059-4.CrossRefPubMed

85.

Schutte SS, Schutte RJ, Barragan EV, O'Dowd DK. Model systems for studying cellular mechanisms of SCN1A-related epilepsy. J Neurophysiol. 2016;115(4):1755–66. https://doi.org/10.1152/jn.00824.2015.CrossRefPubMedPubMedCentral

86.

Devor M. Sodium channels and mechanisms of neuropathic pain. J Pain. 2006;7(1 Suppl 1):S3–s12. https://doi.org/10.1016/j.jpain.2005.09.006.CrossRefPubMed

87.

Dib-Hajj SD, Black JA, Waxman SG. Voltage-gated sodium channels: therapeutic targets for pain. Pain Med (Malden, Mass). 2009;10(7):1260–9. https://doi.org/10.1111/j.1526-4637.2009.00719.x.CrossRef

88.

Waxman SG, Dib-Hajj S. Erythermalgia: molecular basis for an inherited pain syndrome. Trends Mol Med. 2005;11(12):555–62. https://doi.org/10.1016/j.molmed.2005.10.004.CrossRefPubMed

89.

Barros J, Ferreira A, Brandao AF, Lemos C, Correia F, Damasio J, et al. Familial hemiplegic migraine due to L263V SCN1A mutation: discordance for epilepsy between two kindreds from Douro Valley. Cephalalgia. 2014;34(12):1015–20. https://doi.org/10.1177/0333102414527015.CrossRefPubMed

90.

de Vries B, Frants RR, Ferrari MD, van den Maagdenberg AM. Molecular genetics of migraine. Hum Genet. 2009;126(1):115–32. https://doi.org/10.1007/s00439-009-0684-z.CrossRefPubMed

91.

De Vries B, Haan J, Frants RR, Van den Maagdenberg AM, Ferrari MD. Genetic biomarkers for migraine. Headache. 2006;46(7):1059–68. https://doi.org/10.1111/j.1526-4610.2006.00499.x.CrossRefPubMed

92.

Stam AH, van den Maagdenberg AM, Haan J, Terwindt GM, Ferrari MD. Genetics of migraine: an update with special attention to genetic comorbidity. Curr Opin Neurol. 2008;21(3):288–93. https://doi.org/10.1097/WCO.0b013e3282fd171a.CrossRefPubMed

93.

Catterall WA. Dravet syndrome: a sodium channel interneuronopathy. Curr Opinion Physiol. 2018;2:42–50. https://doi.org/10.1016/j.cophys.2017.12.007.CrossRef

94.

Favero M, Sotuyo NP, Lopez E, Kearney JA, Goldberg EM. A transient developmental window of fast-spiking interneuron dysfunction in a mouse model of Dravet syndrome. J Neurosci. 2018;38(36):7912–27. https://doi.org/10.1523/jneurosci.0193-18.2018.CrossRefPubMedPubMedCentral

95.

Lopez-Santiago L, Isom LL. Dravet syndrome: a developmental and epileptic encephalopathy. Epilepsy Curr. 2019;19(1):51–3. https://doi.org/10.1177/1535759718822038.CrossRefPubMedPubMedCentral

96.

Rubinstein M, Patowary A, Stanaway IB, McCord E, Nesbitt RR, Archer M, et al. Association of rare missense variants in the second intracellular loop of NaV1.7 sodium channels with familial autism. Mol Psychiatry. 2018;23(2):231–9. https://doi.org/10.1038/mp.2016.222.CrossRefPubMed

97.

Tatsukawa T, Ogiwara I, Mazaki E, Shimohata A, Yamakawa K. Impairments in social novelty recognition and spatial memory in mice with conditional deletion of Scn1a in parvalbumin-expressing cells. Neurobiol Dis. 2018;112:24–34. https://doi.org/10.1016/j.nbd.2018.01.009.CrossRefPubMed

98.

Black JA, Newcombe J, Waxman SG. Astrocytes within multiple sclerosis lesions upregulate sodium channel Nav1.5. Brain. 2010;133(Pt 3):835–46. https://doi.org/10.1093/brain/awq003.CrossRefPubMed

99.

Zhao S, Tang Z, Xie Q, Wang J, Luo L, Liu Y, et al. Association between epilepsy and risk of sexual dysfunction: a meta-analysis. Seizure. 2019;65:80–8. https://doi.org/10.1016/j.seizure.2019.01.004.CrossRefPubMed

100.

101.

Matos G, Alvarenga TA, Tufik S, Andersen ML. Sexual dysfunction and epilepsy: the reasons beyond medications. Epilepsia. 2013;54(1):205–6. https://doi.org/10.1111/epi.12047.CrossRefPubMed

102.

103.

Morrell MJ. Effects of epilepsy on women's reproductive health. Epilepsia. 1998;39(Suppl 8):S32–7.CrossRefPubMed

104.

Foundation E (2007) Available from: Access date: 4/25/19. https://www.epilepsy.com/learn/professionals/specialized-populations/women/discussion-guide. Accessed 25 April 2019.

105.

Svalheim S, Tauboll E, Bjornenak T, Roste LS, Morland T, Saetre ER, et al. Do women with epilepsy have increased frequency of menstrual disturbances? Seizure. 2003;12(8):529–33.CrossRefPubMed

106.

Harden CL. Issues for mature women with epilepsy. Int Rev Neurobiol. 2008;83:385–95. https://doi.org/10.1016/S0074-7742(08)00021-4.CrossRefPubMed

107.

Andersen ML, Alvarenga TA, Scorza FA, Matos G, Sonoda EY, Hirotsu C, et al. Impairment of sexual function in rats with epilepsy. J Sex Med. 2012;9(9):2266–72. https://doi.org/10.1111/j.1743-6109.2012.02792.x.CrossRefPubMed

108.

Alvarenga TA, Matos G, Scorza FA, Amado D, Cavalheiro EA, Tufik S, et al. Sexual response in female rats with status epilepticus. Epilepsia. 2013;54(4):644–8. https://doi.org/10.1111/epi.12117.CrossRefPubMed

109.

Lofgren E, Mikkonen K, Tolonen U, Pakarinen A, Koivunen R, Myllyla VV, et al. Reproductive endocrine function in women with epilepsy: the role of epilepsy type and medication. Epilepsy Behav. 2007;10(1):77–83. https://doi.org/10.1016/j.yebeh.2006.09.011.CrossRefPubMed

110.

Lossius MI, Tauboll E, Mowinckel P, Morkrid L, Gjerstad L. Reversible effects of antiepileptic drugs on reproductive endocrine function in men and women with epilepsy--a prospective randomized double-blind withdrawal study. Epilepsia. 2007;48(10):1875–82. https://doi.org/10.1111/j.1528-1167.2007.01147.x.CrossRefPubMed

111.

Steinlein OK. Channelopathies can cause epilepsy in man. Eur J Pain. 2002;6(Suppl A):27–34. https://doi.org/10.1053/eujp.2001.0319.

Titel: Exploration of Ion Channels in the Clitoris: a Review
verfasst von: Gabrielle Moore
Zuri Ngozi
Crystal Burgess
Audrey Weber
Stacey Dutton
Publikationsdatum: 18.07.2019
Verlag: Springer US
Erschienen in: Current Sexual Health Reports / Ausgabe 3/2019
Print ISSN: 1548-3584
Elektronische ISSN: 1548-3592
DOI: https://doi.org/10.1007/s11930-019-00206-x

Neu im Fachgebiet Urologie

19.04.2024 | EAU 2024 | Kongressbericht | Nachrichten

Update Urologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Exploration of Ion Channels in the Clitoris: a Review

Abstract

Purpose of the Review

Recent Findings

Summary

Neu im Fachgebiet Urologie

Varikozelen bei Jugendlichen: Das Für und Wider der Operation

Ureterstriktur: Innovative OP-Technik bewährt sich

Prostatakarzinom: EU initiiert neues Screeningkonzept

Blasenkarzinom – Biomarker statt Zytologie?

Update Urologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Purpose of the Review

Recent Findings

Summary

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2019

Plant-Derived Supplements for Sexual Health and Problems: Part 1—Trends over the Past Decade

Preventing Infections in Prosthetic Surgery

Minimizing Sexual Dysfunction in BPH Surgery

Update on Sexual Dysfunction Associated with Psychotropic Medications and Its Treatment

A Review of Female Genital Cutting (FGC) in the Dawoodi Bohra Community:

“A Review of Female Genital Cutting in the Dawoodi Bohra Community: Part 3—the Historical, Anthropological and Religious Underpinnings of FGC in the Dawoodi Bohras”

Neu im Fachgebiet Urologie

Varikozelen bei Jugendlichen: Das Für und Wider der Operation

Ureterstriktur: Innovative OP-Technik bewährt sich

Prostatakarzinom: EU initiiert neues Screeningkonzept

Blasenkarzinom – Biomarker statt Zytologie?

Update Urologie