Comparative effects of a new calcium channel antagonist, mepirodipine, on rabbit spontaneously beating sino-atrial...

The effects of mepirodipine, a new 1,4-dihydropyridine calcium antagonist, on the membrane potentials were examined on spontaneously beating rabbit sino-atrial (SA) node cells and on the membrane currents under voltage-clamped conditions. Mepirodipine 3 x 10(-9) M significantly decreased the action potential amplitude and the maximum rate of depolarization. The action potential duration and the cycle length were prolonged. Sinus arrest occurred at 10(-8) M in all of five preparations. In voltage-clamped SA node cells, mepirodipine in concentrations higher than 3 x 10(-9) M decreased the slow inward current. It did not affect the steady state outward current and the hyperpolarization-activated inward current. Verapamil, diltiazem and nifedipine produced similar changes in the action potential parameters, but at a concentration of 10(-6) M. At concentrations higher than 10(-5) M, they elicited sinus arrest. These results suggest that mepirodipine is a more potent inhibitor of spontaneous calcium-dependent SA node impulse generation than the three other calcium antagonists tested.