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-depend ent L-type Ca2+ channel, certain organic Ca2+ channel antagonists such as n imodipine 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-c ell patch recording under voltage-clamped conditions. Those channels as wel l as L-type Ca2+ channel regulate neuronal electrical activity in central a nd peripheral nervous systems. All blockers tested here showed the channels at micromollar concentrations. The blocking potency for Na+ channel was fl unarizine > nicardipine > nitrendipine > cilnidipine much greater than dilt iazem = verapamil = nifedipine. On the other hand the blocking potency for N-type Ca2+ channel was cilnidipine > flunarizine > nimodipine > nitrendipi ne much greater than verapamil = diltiazem = nifedipine. These non-L-type a ctions 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.