Magnesium shifts voltage dependence of activation of delayed rectifier I(K) in guinea pig ventricular myocytes.
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.
Williams
B A
BA
Bureau of Drug Research, Health Protection Branch, Health Canada, Ottawa, Ontario.
Beatch
G N
GN
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002478:Cells, Cultured; D051668:Delayed Rectifier Potassium Channels; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010627:Phenethylamines / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D051668:Delayed Rectifier Potassium Channels; D010627:Phenethylamines; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides; D008274:Magnesium; D007545:Isoproterenol; C063533:dofetilide