Effects of acute cooling/rewarming on membrane potential and K(+) currents in rat ventricular myocytes.
The effects of acute cooling/rewarming on cardiac K(+) currents and membrane potential were investigated. Membrane potential and current were assessed with whole-cell patch-clamp technique in current- and voltage-clamp modes. When the temperature of bath solution was decreased from 25 °C; to 4 °C, the transient outward current (I(to)) was completely abolished, the sustained outward K(+) current (I(ss)) at +60 mV and the inward rectifier K(+) current (I(K1)) at -120 mV were depressed by (48.5±14.1)% and (35.7±18.2)%, respectively, and the membrane potential became more positive. After the temperature of bath solution was raised from 4 °C; to 36 °C;, the membrane potential exhibited a transient hyperpolarization and then was maintained at a stable level. In some myocytes (36 out of 58), activation of the ATP-sensitive K(+) (K(ATP)) channels after rewarming was observed. The rewarming-induced change in the membrane potential was inhibited by the Na(+)/K(+)-ATPase inhibitor ouabain (100 μmol/L), and the rewarming-elicited activation of K(ATP) channels was inhibited by the protein kinase A inhibitor H-89 (100 μmol/L). Moreover, decrease of the temperature from 25 °C; to 4 °C; did not induce any significant change in cell volume when the cell membrane potential was clamped at 0 mV. However, significant cell shrinkage with spots was observed soon after rewarming-induced activation of K(ATP) channels. These data demonstrate that acute cooling/rewarming has a profound influence on the membrane potential and K(+) currents of ventricular myocytes, and suggest that activation of K(ATP) channels may play a role in cardiac cooling/rewarming injury.
Liaoning Key Laboratory of Biophysics, Institute of Basic Medical Sciences, Medical College, Dalian University, Dalian 116622, China.
Long-Tian
LT
Li
Li-Bin
LB
Zhang
Yan-Li
YL
Si
Fu-Cheng
FC
Xiao
Da
D
Li
Shan
S
Gao
Dong-Liang
DL
Li
Shi-Sheng
SS
Zhou
D000818:Animals; D003080:Cold Temperature; D007546:Isoquinolines / Q000494:pharmacology; D054086:KATP Channels / Q000378:metabolism*; D008564:Membrane Potentials; D032383:Myocytes, Cardiac / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017694:Rewarming; D013449:Sulfonamides / Q000494:pharmacology
D007546:Isoquinolines; D054086:KATP Channels; D013449:Sulfonamides; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide