Effect of TaiCatoxin (TCX) on the electrophysiological, mechanical and biochemical characteristics of spontaneously beating ventricular cardiomyocytes.
TaiCatoxin (TCX), a complex toxin isolated from Taipan snake venom, is believed to have a specific blocking activity on voltage-dependent cardiac calcium channels. The aim of this study was to investigate the effects of TCX on a broad range of heart muscle cell functions, i.e. electrophysiology, contractility, automaticity and the related biochemical modifications. Myocyte-enriched cultures were prepared from newborn rat heart ventricles. The transmembrane potentials were recorded with glass microelectrodes. The contractions were monitored photometrically. TCX decreased the action potential amplitudes, mainly by lowering the plateau. The action potential duration and the contraction parameters were decreased. Although TCX has a minor overall negative chronotropic effect, it evoked transient but severe arrhythmias and prolonged changes in the intercellular electrical coupling. Moreover, the action of TCX appeared to be dose-dependent. These effects are consistent with a specific blockade of the L-type, voltage-dependent calcium channels, but effects of other components of the toxin complex cannot be excluded. TCX also exhibits phospholipase A2 activity leading to the release of Iysophospholipids and FFA (acyl CoA and acyl carnitine), which have detrimental effects on cellular integrity and function.
Laboratory de Physiologie Faculté de Médecine, Dijon, France.
E
E
Fantini
P
P
Athias
R
R
Tirosh
A
A
Pinson
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D004546:Elapid Venoms / Q000494:pharmacology*; D004594:Electrophysiology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D008246:Lysophospholipids / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D004546:Elapid Venoms; D005230:Fatty Acids, Nonesterified; D008246:Lysophospholipids; C079205:taicatoxin