Raising internal potassium concentration from 130 to 170 mM increased Ca2+ influx during action potential clamp by approximately 42% in isolated guinea pig ventricular myocytes.
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.
Linz et al. (Wed,) conducted a other in Myocardial ischemia. Altered internal potassium concentration ([K+]i) vs. Physiological [K+]i was evaluated on L-type calcium current amplitude and Ca2+ influx. Raising internal potassium concentration from 130 to 170 mM increased Ca2+ influx during action potential clamp by approximately 42% in isolated guinea pig ventricular myocytes.
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