The role of extracellular Ca²⁺ in carbachol-induced tonic contraction of the pig detrusor smooth muscle

Abstract

The role of extracellular Ca²⁺ in the toniccontractile response to muscarinic receptor stimulation was investigated in isolated detrusor smooth muscle from the pig urinary bladder.

Carbachol (10⁻⁸ −10⁻⁵ M) produced a concentration-dependent contractile response in isolated pig detrusor smooth muscle strips consisting of an initial phasic component followed by a tonic component. During the plateau of the tonic contractions induced by carbachol at the submaximal concentration of 10⁻⁶ M, the inhibiting effects of atropine, EGTA, nifedipine (a voltage-dependent calcium channel antagonist), H-7 [a protein kinase C (PKC) inhibitor] and YM 934 (a potassium channel opener) on the contractions were evaluated. Atropine (10⁻¹⁰ −3 × 10⁻⁸ M) concentration-dependently inhibited the tonic contractions induced by carbachol. In the same experimental conditions, EGTA (4 mM) and nifedipine (10⁻⁹ −3 × 10⁻⁷ M) depressed the tonic contractions in a concentration-dependent manner as did H-7 (10⁻⁵ −3 × 10⁻⁵ M) and YM934 (10⁻⁸ -10⁻⁶ M). However, H-7 (10⁻⁵-3 × 10⁻⁵ M) and YM934 (10⁻⁶ M) were very weak in inhibiting the contractions induced by KCl (50 mM) in isolated pig detrusor smooth muscle strips.

These results suggest that the tonic-contractile response induced by carbachol in pig detrusor smooth muscle strips is dependent mainly on depolarization of the cell membranes and an influx of extracellular Ca²⁺, and also suggest that this depolarizing response may be due to inactivation of ATP-sensitive potassium channels through muscarinic activation of PKC.