© 1997 by European Society of Cardiology
Copyright © 1997, European Society of Cardiology
Modulation of L-type calcium current by internal potassium in guinea pig ventricular myocytes
Physiological Institute, University of Bonn, Wilhelmstraße 31, D-53111 Bonn, Germany
Objectives: The early phase of myocardial ischemia is characterized by a considerable K+ efflux from cardiac myocytes, causing decreasing internal ([K+]i) and increasing external ([K+]o) K+ concentrations. The change in [K+]i and [K+]o is one of the factors thought to initiate the ischemia-induced changes in electrical activity. Nevertheless, little is known about the influence of [K+]i and [K+]o on the L-type calcium current. Methods: The whole-cell patch-clamp technique combined with an internal perfusion system was used to test possible actions of altered [K+]i and [K+]o on L-type current carried by Ca2+ and Ba2+ in isolated guinea pig ventricular myocytes. Results: Changing the [K+]i in the range of 110–170 mM revealed a sigmoidal concentration-response relationship between the L-type current and [K+]i. The maximum change in current amplitude was more than 40% with a half-saturation concentration of 136 mM which is near the physiological [K+]i. Ca2+ influx during action potential clamp increased by approximately 42% after raising [K+]i from 130 to 170 mM. Internal perfusion with Cs+ demonstrated that Cs+ is less effective than K+ in regulating the L-type current. By using ATP-analogues, [K+]i was shown to affect the L-type channel in a phosphorylation-independent way. Changes in [K+]o only modulated the L-type current via alterations in [K+]i. Conclusions: The decrease in [K+]i during early ischemia is, per se, sufficient to reduce the L-type current by up to 15%, thereby decreasing the action potential duration, and Ca2+ influx into the cells. This may act in addition to well-known mechanisms such as changes in internal pH and falling ATP levels, which influence the L-type current. Moreover, the phenomenon may complicate the interpretation of electrophysiological measurements of L-type current under conditions where [K+]i is not precisely controlled.
KEYWORDS Myocardial ischemia; Calcium current, L-type; Potassium concentration, external; Potassium concentration, internal; Guinea pig, ventricular myocytes; Patch-clamp
* Corresponding author. Tel. +49 228 287-2311; Fax +49 228 287-2313; E-mail: meyer@snphysio2.wilhelm.uni-bonn.de
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