Dihydropyridine BAY-K-8644 activates chromaffin cell calcium channels

Douglas and Rubin suggested that "the role of acetylcholine as a transmitter at the adrenal medulla is to cause some brief change in medullary cells which allows Ca ions to penetrate them and trigger the catecholamine ejection process". The Ca2+-channel blocking agents, verapamil, nifedipine and nitrendipine, have been used widely to investigate the properties of slow Ca2+ channels in a variety of tissues, including the adrenomedullary chromaffin cell. Recently, small modifications to the nifedipine molecule produced a derivative, BAY-K-8644 (methyl-1,4-dihydro-2, 6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5-carboxylate), that in contrast to the Ca2+-channel blocking agents, stimulated cardiac and vascular smooth muscle contractility. We have tested whether this compound behaves as a Ca2+-channel activator at the chromaffin cell membrane as shown by Schramm et al. in smooth muscle cells. The experiments described here strongly suggest that it does so.