AJP - Heart and Circulatory Physiology, Vol 272, Issue 3 1292-H1301, Copyright © 1997 by American Physiological Society
Magnesium shifts voltage dependence of activation of delayed rectifier I(K) in guinea pig ventricular myocytes
B. A. Williams and G. N. Beatch
Bureau of Drug Research, Health Protection Branch, Health Canada, Ottawa, Ontario.
The sensitivity of the delayed rectifier K+ current (I(K)) to intracellular
Mg2+ was investigated in guinea pig ventricular myocytes using the whole
cell patch-clamp technique. An increase in free intracellular Mg2+
concentration ([Mg2+]i) led to a dose-dependent decrease in I(K) with a
half-maximal effect of approximately 20 nM. Activation of I(K) was shifted
toward more positive voltages on increasing [Mg2+]i, but little effect was
observed on activation and deactivation kinetics. Isoproterenol increased
I(K) and was partially reversible in both control and 100 nM [Mg2+]i. The
antiarrhythmic drug dofetilide was used to separate I(K) into its two
components, rapidly activating (I(Kr)) and slowly activating (I(Ks)). The
magnitude of both components decreased to a similar extent with an increase
in [Mg2+]i. As [Mg2+]i was reduced, however, the number of experiments in
which the dofetilide-sensitive current I(Kr) displayed inward rectification
was reduced. In contrast to results previously reported for frog myocytes,
it is unlikely that Mg2+ effects on guinea pig I(K) are mediated by a
protein phosphatase.
