Reduction of calcium-independent transient outward potassium current density in DOCA salt hypertrophied rat ventricular myocytes.
Saline-drinking, left-nephrectomized rats made hypertensive by deoxycorticosterone acetate (DOCA) pellet implantation at the time of surgery develop a cardiac hypertrophy, which becomes maximal after 6-7 weeks. The hypertrophy results in a marked increase in the amplitude and duration of both the early and the late component of the ventricular action potential plateau recorded in the isolated perfused rat heart. The 4-aminopyridine(4-AP)-sensitive calcium-independent transient outward potassium current was markedly depressed in hypertrophied ventricular myocytes resulting in a highly significant decrease in current density (from 19.9 +/- 3.5 to 6.4 +/- 3.1 pA/pF at +60 mV). Activation/voltage and steady-state inactivation/voltage relationships were moderately although non-significantly shifted towards negative potentials. The steady-state outward current measured at the end of 1-s depolarizing pulses was not significantly changed in hypertrophied myocytes. 4-AP induced a smaller increase in plateau amplitude and duration in hypertrophied rather than in control hearts, a point that is well explained by the depression of the transient outward current resulting from hypertrophy. We also demonstrated that a complete recovery of both cell capacitance and transient outward current amplitude occurs in myocytes from saline-drinking rats studied 13 weeks after DOCA pellet implantation, showing that hypertrophy regresses as a result of pellet elimination. Several mechanisms can be involved in the observed phenomena, including the possibility that the expression of potassium channels responsible for the transient outward current is not enhanced by hypertrophy in contrast with what occurs in the case of calcium channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Coulombe
A
A
Laboratoire de Physiologie Cellulaire, URA CNRS 1121, Université Paris-Sud, Orsay, France.
Momtaz
A
A
Richer
P
P
Swynghedauw
B
B
Coraboeuf
E
E
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D006332:Cardiomegaly / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D003900:Desoxycorticosterone; D004553:Electric Conductivity; D006706:Homeostasis; D008297:Male; D009206:Myocardium / Q000473:pathology; D009392:Nephrectomy; D011188:Potassium / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride; D016276:Ventricular Function
D003900:Desoxycorticosterone; D012965:Sodium Chloride; D011188:Potassium; D002118:Calcium