Physiological and pharmacological correlates of calcium antagonist receptors.
We studied voltage-sensitive and Na-dependent Ca2+ flux into synaptosomes as well as Na-dependent influx in cardiac sarcolemmal vesicles. Rapid, voltage-sensitive 45Ca2+ influx into synaptosomes is blocked by cadmium (IC50 1 microM) and the novel peptide toxin omega-conotoxin GVIA (30% of uptake blocked by 50 pM toxin), but not by dihydropyridine and phenylalkylamine calcium antagonists, even though [3H]dihydropyridines and [3H]phenylalkylamines bind to synaptosomes. The toxin also blocks voltage-sensitive neurotransmitter release from synaptosomes. Sodium-dependent Ca2+ flux into synaptosomes and cardiac sarcolemmal vesicles is inhibited by selected antihistamines, neuroleptics, and tricyclic antidepressants. We can elicit neurotransmitter release from synaptosomes by changing the Na gradient; this neurotransmitter release is absolutely Ca2+-dependent and blocked by Na+/Ca2+ exchange inhibitors, thereby suggesting that physiological neurotransmitter release may have a Na+/Ca2+ exchange component. More potent Na+/Ca2+ exchange inhibitors may have cardiovascular roles as inotropic agents or antagonists of calcium-related injury to cardiomyocytes during reperfusion or other disease states.
Wagner
J A
JA
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Reynolds
I J
IJ
Snyder
S H
SH
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics / Q000494:pharmacology*; D015220:Calcium Channels; D006321:Heart / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology; D009568:Nitrendipine / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007473:Ion Channels; D008978:Mollusk Venoms; D011978:Receptors, Nicotinic; D020866:omega-Conotoxin GVIA; D009568:Nitrendipine; D012964:Sodium; D002118:Calcium