Wortmannin inhibits contraction without altering electrical activity in canine gastric smooth muscle

Wortmannin, an inhibitor of myosin light-chain kinase (10-30 mu M), completely and irreversibly abolished (in 75% of tissues from canine gastric antrum) phasic contractions caused by slow waves with no significant effects on resting membrane potential or the frequency, amplitude, or duration of spontaneous slow waves. Responses to agents that normally cause hyperpolarization (cromakalim, sodium nitroprusside, and forskolin) were unaffected by wortmannin treatment. It was also possible to study the excitatory effects of agents and conditions that normally result in loss of intracellular impalements: 1) elevated extracellular K+ concentrations altered membrane potential close to values predicted by the Nernst equation, and 2) high concentrations of acetylcholine produced depolarization and rapid oscillations in membrane potential coincident with contractile activity. Cholinergic increases in myosin light-chain phosphorylation and contractions were partially blocked by wortmannin. In canine antrum, wortmannin inhibition of contraction was irreversible, although in other tissue types, partial recovery of contractions was observed when wortmannin was removed. Wortmannin can be a useful agent to investigate the electrophysiology of some smooth muscles when movement might lead to recording artifacts or loss of signal.