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1 Department of Physiology, Faculty of Medicine, Saga University, Saga 849-8501, Japan
The strong inward rectification of the whole cell Kir2.1 current, which is very similar to the cardiac inward rectifier K+ current (IK1), is caused by voltage-dependent blockade of outward currents by the intracellular polyamines spermine and spermidine. We recently showed that macroscopic Kir2.1 currents obtained from inside-out patches in the presence of various concentrations of cytoplasmic polyamines are well explained by the sum of the currents through two populations of channels that show differing susceptibilities to polyamine blockade. The outward currents obtained with 5–10 µM cytoplasmic spermine showed current–voltage relationships similar to those of IK1 and were considered to flow mostly through a small population of channels exhibiting lower spermine sensitivity. Here we used inside-out patches to examine the blockade of macroscopic Kir2.1 currents by cytoplasmic Mg2+ in the absence and presence of cytoplasmic spermine. Outward currents were blocked by 0.6 and 1.1 mM Mg2+ in a concentration-dependent manner, but a small fraction (
0.1) of the macroscopic conductance was resistant to Mg2+ at those concentrations, suggesting there are two populations of Kir2.1 channels with different sensitivities to Mg2+. Furthermore, at those concentrations, Mg2+ blocked inward currents by inducing a shallow blocked state that differed from the deeper state causing the inward rectification. In the presence of 1.1 mM Mg2+
+ 5 µM spermine, Mg2+ blocked a substantial current component during depolarizing pulses and generated transient outward components, which is consistent with findings from earlier whole-cell experiments. In the steady state, Mg2+ blocked the currents at voltages around and negative to the reversal potential and induced sustained outward components. The steady-state and time-dependent current amplitudes and the fractional blockades caused by spermine and Mg2+ could be quantitatively explained by a model in which Mg2+ competes with spermine to block the high-affinity channel and induces three conductance states. The present results suggest that the outward IK1 flows through two populations of channels with different sensitivities to cytoplasmic blockers.
(Received 16 November 2004;
accepted after revision 21 December 2004;
first published online 23 December 2004)
Corresponding author K. Ishihara: Department of Physiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan. Email: keiko{at}med.saga-u.ac.jp
This article has been cited by other articles:
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  K. Ishihara and D.-H. Yan Low-affinity spermine block mediating outward currents through Kir2.1 and Kir2.2 inward rectifier potassium channels J. Physiol., September 15, 2007; 583(3): 891 - 908. [Abstract] [Full Text] [PDF]
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B. K. Panama and A. N. Lopatin Differential polyamine sensitivity in inwardly rectifying Kir2 potassium channels J. Physiol., March 1, 2006; 571(2): 287 - 302. [Abstract] [Full Text] [PDF]
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D.-H. Yan, K. Nishimura, K. Yoshida, K. Nakahira, T. Ehara, K. Igarashi, and K. Ishihara Different intracellular polyamine concentrations underlie the difference in the inward rectifier K+ currents in atria and ventricles of the guinea-pig heart J. Physiol., March 15, 2005; 563(3): 713 - 724. [Abstract] [Full Text] [PDF]
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