Inhibition of Ca2+ current in ileal cells by cyclopiazonic acid and ryanodine.

The effects of cyclopiazonic acid and its combination with ryanodine on the inward Ca2+ current (ICa) were investigated in smooth muscle cells isolated from the circular layer of guinea-pig ileum. The ICa of these cells exhibited two components: a low-threshold, nicardipine (5 microM)-resistant, fast-inactivating component and a high-threshold, nicardipine-blockable and slowly inactivating component. Neither cyclopiazonic acid (up to 10 microM) nor ryanodine (10 microM) was able to affect both these components of ICa, when applied separately. Cyclopiazonic acid and ryanodine combination led to total abolishment of the high-threshold component, leaving the low-threshold component unaffected. The data presented suggest a process of Ca(2+)-dependent inactivation of the high-threshold component, elicited by an increase in the subplasmalemmal Ca2+ concentration due to Ca2+ released from the sarcoplasmic reticulum. It is considered that the combination of cyclopiazonic acid and ryanodine can be used as a valuable method to study the calcium sensitivity of both components of the ICa.