Effect of tetrodotoxin, lidocaine, and quinidine on the transient inward current of sheep Purkinje fibres

Abstract

The effect of tetrodotoxin (TTX), lidocaine, and quinidine on the transient inward current (TI) was studied in voltage-clamped sheep cardiac Purkinje fibres. The TI was induced by elevation of extracellular Ca or addition of strophanthidin. Reduction of external Na had a biphasic effect on the steady state TI magnitude; a moderate (less than 50%) reduction of external Na had an enhancing effect on the TI; a further decrease of extracellular Na was accompanied by a decline of TI amplitude. The TI could not be induced in Na-free medium (external Ca less than or equal to 9.0 mM). TTX, lidocaine, and quinidine reduced the magnitude of the TI in a dose-dependent way. The blocking effect of these agents could be compensated for by a moderate (less than 50%) reduction of external Na or an elevation of extracellular Ca. It is suggested that the blocking effect of TTX, lidocaine, and quinidine on the TI is due to a reduction of intracellular Na, which causes a decay of intracellular Ca via the Na-Ca exchange mechanism.

Mode‐dependent inhibition by quinidine of Na+–Ca2+ exchanger current from guinea‐pig isolated ventricular myocytes

“…Quinidine can inhibit cardiac L‐type Ca current (I Ca,L ) 11,12 . The agent has also been reported to suppress delayed afterdepolarizations (DAD) from canine and sheep Purkinje fibres induced by Na + –K + pump inhibition 13,14 . The Na + –Ca 2+ exchanger is a membrane protein that plays important roles in Ca 2+ homeostasis and the profile of cardiac action potentials 15,16 .…”