[Electrophysiological effects of changrolin on single ventricular myocytes isolated from adult guinea pig].

Calcium tolerant single ventricular cardiomyocytes were dispersed from adult guinea pig hearts by retrograde perfusion with collagenase solution. More than 50% of the isolated cells retained rod shaped configuration and showed normal electrical activities with resting potentials (RP) at -82 +/- 2 mV and action potential amplitude (APA) at 116 +/- 6 mV. The effects of changrolin (CRL, 4-[3', 5'-bis [(N-pyrrolidinyl)-methyl]-4'-hydroxyanilino]-quinazoline) on the transmembrane action potentials of the single cells were measured with intracellular glass microelectrodes. At the concentration of 50 mumol/L, CRL caused profound reductions of APA, maximal rate of phase 0 depolarization (Vmax), and action potential duration (APD). The effective refractory period (ERP) was prolonged. The action of CRL on Vmax showed use- and frequency-dependences. Trains of stimuli in the studied range of frequencies led to an exponential decline in Vmax to a new plateau and the maximal reduction was at the highest frequency. At 1 Hz, the onset rate of this action was 0.036 +/- 0.004 AP-1. CRL did not cause a resting state block of Vmax. These findings suggest that CRL is a slow type, class I anti-arrhythmia drug.