Non-L-type actions of organic Ca2+ channel blockers:: Implications for Na+ and N-type Ca2+ channels blockades

In addition to their well characterized interaction with the voltage-dependent L-type Ca2+ channel, certain organic Ca2+ channel antagonists such as nimodipine and flunarizine have been reported to modulate a wide variety of cellular functions as diverse as blockades of Na+ and K+ channels. In this study, we re-examined effects of four types Ca2+ channel blockers on non-L-type (voltage-dependent Na+ and N-type Ca2+) channels, by using the whole-cell patch recording under voltage-clamped conditions. Those channels as well as L-type Ca2+ channel regulate neuronal electrical activity in central and peripheral nervous systems. All blockers tested here showed the channels at micromollar concentrations. The blocking potency for Na+ channel was flunarizine > nicardipine > nitrendipine > cilnidipine much greater than diltiazem = verapamil = nifedipine. On the other hand the blocking potency for N-type Ca2+ channel was cilnidipine > flunarizine > nimodipine > nitrendipine much greater than verapamil = diltiazem = nifedipine. These non-L-type actions of organic Ca2+ channel blockers might explain a wide variety of non-cardiovascular effects that had not been simply understood by their L-type Ca2+ channel blocking actions.