Aging-associated changes in whole cell K(+) and L-type Ca(2+) currents in rat ventricular myocytes.
The effect of aging on cardiac membrane currents remains unclear. This study examined the inward rectifier K(+) current (I(K1)), the transient outward K(+) current (I(to)), and the L-type Ca(2+) channel current (I(Ca,L)) in ventricular myocytes isolated from young adult (6 mo) and aged (>27 mo) Fischer 344 rats using whole cell patch-clamp techniques. Along with an increase in the cell size and membrane capacitance, aged myocytes had the same magnitude of peak I(K1) with a greater slope conductance but displayed smaller steady-state I(K1). Aged myocytes also had a greater I(to) with an increased rate of activation, but the I(to) inactivation kinetics, steady-state inactivation, and responsiveness to L-phenylephrine, an alpha(1)-adrenergic agonist, were unaltered. The magnitude of peak I(Ca,L) in aged myocytes was decreased and accompanied by a slower inactivation, but the I(Ca,L) steady-state inactivation was unaltered. Action potential duration in aged myocytes was prolonged only at 90% of full repolarization (APD(90)) when compared with the action potential duration of young adult myocytes. Aged myocytes from Long-Evans rats showed similar changes in I(to) and I(Ca,L) but an increased I(K1). These results demonstrate aging-associated changes in action potential, in morphology, and in I(K1), I(to), and I(Ca,L) of rat ventricular myocytes that possibly contribute to the decreased cardiac function of aged hearts.
Liu
S J
SJ
Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. LiuShi@exchange.uams.edu
Wyeth
R P
RP
Melchert
R B
RB
Kennedy
R H
RH
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D048429:Cell Size / Q000502:physiology; D002478:Cells, Cultured; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000502:physiology; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D020746:Calcium Channels, L-Type; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018340:Receptors, Adrenergic, alpha-1