Kw. Linz et R. Meyer, MODULATION OF L-TYPE CALCIUM CURRENT BY INTERNAL POTASSIUM IN GUINEA-PIG VENTRICULAR MYOCYTES, Cardiovascular Research, 33(1), 1997, pp. 110-122
Objectives: The early phase of myocardial ischemia is characterized by
a considerable K+ efflux from cardiac myocytes, causing decreasing in
ternal ([K+](i)) and increasing external ([K+](o)) K+ concentrations.
The change in [K+](i) and [K+](o) is one of the factors thought to ini
tiate the ischemia-induced changes in electrical activity. Nevertheles
s, 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 c
ombined with an internal perfusion system was used to test possible ac
tions of altered [K+](i) and [K+](o) on L-type current carried by Ca2 and Ba2+ in isolated guinea pie ventricular myocytes. Results: Changi
ng the [K+](i) in the range of 110-170 mM revealed a sigmoidal concent
ration-response relationship between the L-type current and [K+](i). T
he maximum change in current amplitude was more than 40% with a half-s
aturation concentration of 136 mM which is near the physiological [K+]
(i). Ca2+ influx during action potential clamp increased by approximat
ely 42% after raising [K+](i) from 130 to 170 mM. Internal perfusion w
ith Cs+ demonstrated that Cs+ is less effective than K+ in regulating
the L-type current. By using ATP-analogues. [K+](i) was shown to affec
t 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 decreas
ing thr action potential duration, and Ca2+ influx into the cells. Thi
s may act in addition to well-known mechanisms such as changes in inte
rnal pH and falling ATP levels, which influence the L-type current. Mo
reover, the phenomenon may complicate the interpretation of electrophy
siological measurements of L-type current under conditions where [K+](
i) is nor precisely controlled.