High affinity block of myocardial L-type calcium channels by the spider toxin omega-Aga-toxin IIIA: advantages over 1,4-dihydropyridines

CJ Cohen, EA Ertel, MM Smith, VJ Venema, ME Adams and MD Leibowitz

Department of Membrane Biochemistry and Biophysics, Merck Research Laboratories, Rahway, New Jersey 07065.

The peptide omega-agatoxin IIIA (omega-Aga-IIIA) from venom of the funnel web spider Agelenopsis aperta blocks L-type Ca2+ channels in neurons and myocardial cells with high affinity. We report that omega- Aga-IIIA also blocks whole-cell Ca2+ channel currents in guinea pig atrial myocytes. Although other high affinity blockers of L-type Ca2+ channels are available (such as the 1,4-dihydropyridines), omega-Aga- IIIA is a valuable pharmacological tool; omega-Aga-IIIA is the only known ligand that blocks L-type Ca2+ channels with high affinity at all voltages (IC50 approximately 1 nM) and it causes little or no block of T-type Ca2+ channels, unlike the 1,4-dihydropyridines. We use omega-Aga- IIIA to selectively eliminate L-type Ca2+ currents and we show that felodipine blocks T-type Ca2+ currents. Consequently, the toxin is better than dihydropyridines for separating ionic currents through voltage-dependent Ca2+ channels and defining their physiological function.

Volume 42, Issue 6, pp. 947-951, 12/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics