Diltiazem Facilitates Inactivation of Single L-type Calcium Channels in Guinea Pig Ventricular Myocytes

摘要: Diltiazem is a benzothiazepine Ca2+ channel blocker used clinically for its antihypertensive and antiarrhythmic effects. We studied the mechanism of diltiazem blockade by recording L-type currents from cell-attached patches in isolated guinea pig ventricular myocytes using Ba2+ as charge carrier. With (200 μM) superfusate, multichannel showed use-dependent decline amplitude reflecting reductions numbers superpositions openings. Analysis single-channel revealed that both open closed times were little affected (50 100 μM). However, rate decay averaged current during 150-ms depolarization steps was significantly accelerated state probability containing-sweeps decreased diltiazem, suggesting drug accelerates transition activated to inactivated state. The effect dil-tiazem on slow gating process repetitively applying 500-1000 step pulses at selected holding potentials. Decreased availability reflected increasing number blank sweeps per run depolarized These results suggest reduces influx accelerating inactivation action potentials, due increases channels sustained