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Two Kir2.1 channel populations with different sensitivities to Mg 2+ and polyamine block: a model for the cardiac strong inward rectifier K + channel
Author(s) -
Yan DingHong,
Ishihara* Keiko
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.079186
Subject(s) - spermine , polyamine , inward rectifier potassium ion channel , biophysics , depolarization , conductance , spermidine , chemistry , intracellular , blockade , cytoplasm , patch clamp , biology , ion channel , biochemistry , physics , enzyme , condensed matter physics , receptor
The strong inward rectification of the whole cell Kir2.1 current, which is very similar to the cardiac inward rectifier K + current ( I K1 ), 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 μ m cytoplasmic spermine showed current–voltage relationships similar to those of I K1 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 Mg 2+ in the absence and presence of cytoplasmic spermine. Outward currents were blocked by 0.6 and 1.1 m m Mg 2+ in a concentration‐dependent manner, but a small fraction (∼0.1) of the macroscopic conductance was resistant to Mg 2+ at those concentrations, suggesting there are two populations of Kir2.1 channels with different sensitivities to Mg 2+ . Furthermore, at those concentrations, Mg 2+ 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 m m Mg 2+ + 5 μ m spermine, Mg 2+ 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, Mg 2+ 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 Mg 2+ could be quantitatively explained by a model in which Mg 2+ competes with spermine to block the high‐affinity channel and induces three conductance states. The present results suggest that the outward I K1 flows through two populations of channels with different sensitivities to cytoplasmic blockers.