Blockade of Ca2+ and K+ currents in bag cell neurons of Aplysia californica by dihydropyridine Ca2+ antagonists.
The effects of dihydropyridine calcium antagonists on whole-cell Ca2+ and K+ currents in the neurosecretory bag cells of the marine mollusc Aplysia californica have been investigated. Nifedipine and nisoldipine blocked bag cell Ca2+ currents with effects similar to those seen previously on Ca2+ currents in cardiac muscle: both compounds appeared to interact with Ca2+ channels when they were closed, open, and inactivated. Also, as seen in cardiac cells, nifedipine apparently binds with higher affinity to Ca2+ channels when they are inactivated than when they are either closed or open. Nifedipine and nisoldipine also inhibited 2 outward K+ currents in bag cells: the "delayed rectifier" (IK) and the "A" (IA) currents. Half-maximal blockade of Ca2+ currents occurred at approximately 1.4 microM nifedipine, compared to approximately 3-5 microM for half-maximal blockade of IK and IA. The effects of these compounds on bag cell Ca2+ and K+ currents are interpreted and discussed here in terms of the "modulated receptor" model of drug action. In contrast, however, no measurable effects of nifedipine or nisoldipine were seen on Ca2+ (and/or K+) currents in several vertebrate neuronal cell types. Our results suggest that there are likely to be structural and/or conformational variations in Ca2+ channels in different cells, tissues, and/or species and also that, in some cells, Ca2+ and K+ channels might be structurally similar. These findings also suggest, therefore, that if dihydropyridine binding is used to identify Ca2+ channels, care should be taken to ensure that binding correlates closely with the Ca2+ channels of interest.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D001048:Aplysia; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines; D007473:Ion Channels / Q000187:drug effects* / Q000528:radiation effects; D007700:Kinetics; D008433:Mathematics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015737:Nisoldipine; D011188:Potassium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007473:Ion Channels; D011725:Pyridines; D015737:Nisoldipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D009543:Nifedipine; D011188:Potassium; D002118:Calcium