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.