Modification of Na channel inactivation by alpha-chymotrypsin in single cardiac myocytes.
The effects of alpha-chymotrypsin and trypsin on the macroscopic Na current in isolated guinea pig ventricular myocytes at 16 degrees C were investigated using the whole-cell voltage-clamp technique. Intracellular application of both enzymes reduced the extent of Na current inactivation during 20- to 50-ms depolarizing pulses. Elimination of fast inactivation by alpha-chymotrypsin was accompanied by a slowing of the rate of Na current decay through changes in both the time constants of current decay and the proportions of current undergoing a fast vs slow rate of decay. Treatment that reduced Na current decay to less than or equal to 10% within 20 ms was accompanied by a hyperpolarizing shift of the Na conductance/voltage relationship and an increase in the time-to-peak current that was most prominent for small depolarizations. Evidence for a significant slow inactivation process was obtained following removal of fast inactivation. The effect of trypsin (0.15-0.3 mg/ml) was less specific than alpha-chymotrypsin in that it also reduced Na conductance and increased leak current.
Clarkson
C W
CW
Department of Pharmacology, School of Medicine, Tulane University, New Orleans, LA 70112.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002918:Chymotrypsin / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology* / Q000648:ultrastructure; D012964:Sodium / Q000493:pharmacokinetics; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D014357:Trypsin / Q000494:pharmacology
D000596:Amino Acids; D015222:Sodium Channels; D012964:Sodium; D002918:Chymotrypsin; D014357:Trypsin