The role of extracellular Ca in carbachol-induced tonic contraction of the pig detrusor smooth muscle.

The role of extracellular Ca in the toniccontractile response to muscarinic receptor stimulation was investigated in isolated detrusor smooth muscle from the pig urinary bladder. Carbachol (10 −10 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 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 −3 × 10 M) concentration-dependently inhibited the tonic contractions induced by carbachol. In the same experimental conditions, EGTA (4 mM) and nifedipine (10 −3 × 10 M) depressed the tonic contractions in a concentration-dependent manner as did H-7 (10 −3 × 10 M) and YM934 (10 -10 M). However, H-7 (10-3 × 10 M) and YM934 (10 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 Ca, and also suggest that this depolarizing response may be due to inactivation of ATP-sensitive potassium channels through muscarinic activation of PKC. [ABSTRACT FROM AUTHOR]