The gerbil spiral modiolar artery (SMA) originates via the anterior inferior cerebellar artery from the basilar artery and provides the blood supply to the cochlea. It has an outer diameter of ~60 μm and follows the eighth cranial nerve from the brain stem to the modiolus of the cochlea [
1]. The SMA is an end-artery that feeds the capillary networks of the spiral ligament and the stria vascularis, which maintains the endocochlear potential essential for hearing [
2]. This energy-intensive mechanism renders the cochlea vulnerable to ischemia, which is thought to be involved in the pathogenesis of hearing loss and tinnitus. Consequently, the mechanisms that regulate the diameter of the SMA and thereby cochlear blood flow are of great interest.
Vascular tone is determined by the contractility of the smooth muscle cell, which is regulated by membrane-potential and Ca
2+-dependent as well as independent mechanisms [
3]. An important regulator of smooth muscle contractility is the ryanodine receptor (RyR) mediated "Ca
2+ spark". Ca
2+ sparks are the physical manifestation of coordinated openings of clustered RyRs causing a highly localized and transient increase in the Ca
2+ concentration in the subsarcolemmal space [
4]. Ca
2+ sparks have been demonstrated in all muscle cells - cardiac, skeletal as well as smooth muscle cells. In cardiac and skeletal muscle cells, tight coupling between sarcolemmal voltage-dependent Ca
2+ channels (VDCCs) in the T-tubules and RyRs in the terminal cisternae generates a depolarization-induced Ca
2+-induced-Ca
2+-release (CICR) process that causes contraction [
4]. On the other hand, in smooth muscle cells, particularly in vascular smooth muscle cells, RyRs, large-conductance calcium- and voltage-activated K
+ (BK) channels and VDCCs have been shown to form a functional triad that maintains or mediates vasodilation by limiting Ca
2+ influx via VDCCs [
5‐
8]. Increases in the Ca
2+ concentration in the subsarcolemmal space caused by Ca
2+ sparks, which engulf the cytosolic face of BK channels, cause activation of these channels and hyperpolarization of the membrane potential, closure of VDCCs and vasodilation via a decrease in the cytosolic Ca
2+ concentration in the vicinity of the contractile myofilaments. Thus, Ca
2+ sparks form a negative feedback mechanism that regulates vascular tone and hence blood flow. This mechanism has not yet been identified in the regulation of cochlear blood flow. Previous studies from our lab have indicated the presence of a ryanodine-sensitive Ca
2+ sensing receptor in vascular smooth muscle cells that regulates the contractility of the gerbil SMA [
9]. A role for RyR-mediated Ca
2+ release in hyperpolarization of smooth muscle cells, mediated by activation of BK channels, has been previously suggested in guinea-pig SMA [
10].