WORTMANNIN INHIBITS CONTRACTION WITHOUT ALTERING ELECTRICAL-ACTIVITY IN CANINE GASTRIC SMOOTH-MUSCLE

Wortmannin, an inhibitor of myosin light-chain kinase (10-30 mu M), co mpletely and irreversibly abolished (in 75% of tissues from canine gas tric antrum) phasic contractions caused by slow waves with no signific ant effects on resting membrane potential or the frequency, amplitude, or duration of spontaneous slow waves. Responses to agents that norma lly cause hyperpolarization (cromakalim, sodium nitroprusside, and for skolin) 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 extracellula r K+ concentrations altered membrane potential close to values predict ed 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 wa s irreversible, although in other tissue types, partial recovery of co ntractions was observed when wortmannin was removed. Wortmannin can be a useful agent to investigate the electrophysiology of some smooth mu scles when movement might lead to recording artifacts or loss of signa l.