Regulation of the cardiac delayed rectifier K current by neurotransmitters and magnesium.

Abstract

The delayed rectifier K current plays an important role in cardiac electrophysiology: It is involved in the repolarization of the action potential and in frequency-dependent changes in action potential duration and waveform. The delayed rectifier current IK is regulated by the autonomic nervous system: Beta-adrenergic agonists increase IK. This increase is due to an increase in the maximally activatable current as well as a shift of the activation curve to more negative potentials. Thus, in response to sympathetic nerve stimulation, the action potential would be expected to repolarize more rapidly as a result of activation of more IK current and its activation at more negative potentials. Single-channel analysis suggests that the increase in IK is due to an increase in the availability of IK channels to respond to depolarization. IK is also regulated by internal free Mg2+. When the internal solution contains high [Mg2+], IK decreases, whereas low [Mg2+] results in an increase in current. The effect of Mg2+ is not detectably voltage dependent, suggesting that the mechanism of Mg2+ action involves an allosteric or enzymatic effect. Mg2+ also affects the rate of washout of the response to beta-adrenergic agonists, suggesting that Mg2+ may be affecting the activity of a protein phosphatase.