Differential effects of chronic membrane depolarization on the K+ channel activities in cultured rat ventricular cells.
OBJECTIVE
Although there is widespread interest in the regulation of K+ channel gene expression by membrane depolarization, its effects on cardiac ion channel activity remain unclear. In the present study, we investigated the influences of chronic membrane depolarization on the functional expression of K+ channels in cultured rat cardiomyocytes.


METHODS
Single ventricular cells isolated from day-old rat hearts were cultured for nearly 10 days. From day 6, chronic depolarization induced by elevating the K+ concentration of growth medium to 20 mM was developed for 72 h. Whole-cell patch-clamp techniques were used to record action potentials and ion currents.


RESULTS
Compared with controls, longer action potential durations associated with relatively positive resting potentials were observed after 72-h high K+ incubation. Chronic membrane depolarization caused a significantly reduced density of transient outward current (Ito) without affecting the channel kinetics and voltage-dependence. Delayed rectifier K+ current (IK) in cultured cells could be inhibited by E-4031, showing the drug-sensitive and -resistant components with different kinetic properties. The E-4031-sensitive current activated rapidly, and the drug-resistant current was characterized by slow activation. Both the rapid (IKr) and slow (IKs) components constituted IK recorded from the control and depolarization-treated cells, while in the latter group the current density of IKr was slightly increased and that of IKs was enhanced by 80% with a small hyperpolarizing shift (5 mV) in the voltage-dependent activation curve.


CONCLUSIONS
These observations suggest that the effects of chronic membrane depolarization differ depending on the phenotype of the cardiac K+ channels.
Guo
W
W
Department of Circulation, Nagoya University, Japan. g940015d@eds.ecip.nagoya-u.ac.jp
Kamiya
K
K
Toyama
J
J
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002478:Cells, Cultured; D006321:Heart / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D015221:Potassium Channels; D011725:Pyridines; C063968:E 4031; D011188:Potassium