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Department of Physiology, Saga Medical School, Saga 849-8501, Japan
The strong inward rectifier K+ current, IK1, shows significant outward current amplitude in the voltage range near the reversal potential and thereby causes rapid repolarization at the final phase of cardiac action potentials. However, the mechanism that generates the outward IK1 is not well understood. We recorded currents from the inside-out patches of HEK 293T cells that express the strong inward rectifier K+ channel Kir2.1 and studied the blockage of the currents caused by cytoplasmic polyamines, namely, spermine and spermidine. The outward current–voltage (I–V) relationships of Kir2.1, obtained with 5–10µM spermine or 10–100µM spermidine, were similar to the steady-state outward I–V relationship of IK1, showing a peak at a level that is 
20mV more positive than the reversal potential, with a negative slope at more positive voltages. The relationships exhibited a plateau or a double-hump shape with 1µM spermine/spermidine or 0.1µM spermine, respectively. In the chord conductance–voltage relationships, there were extra conductances in the positive voltage range, which could not be described by the Boltzmann relations fitting the major part of the relationships. The extra conductances, which generated most of the outward currents in the presence of 5–10µM spermine or 10–100µM spermidine, were quantitatively explained by a model that considered two populations of Kir2.1 channels, which were blocked by polyamines in either a high-affinity mode (Mode 1 channel) or a low-affinity mode (Mode 2 channel). Analysis of the inward tail currents following test pulses indicated that the relief from the spermine block of Kir2.1 consisted of an exponential component and a virtually instantaneous component. The fractions of the two components nearly agreed with the fractions of the blockages in Mode 1 and Mode 2 calculated by the model. The estimated proportion of Mode 1 channels to total channels was 0.9 with 0.1–10µM spermine, 0.75 with 1–100µM spermidine, and between 0.75 and 0.9 when spermine and spermidine coexisted. An interaction of spermine/spermidine with the channel at an intracellular site appeared to modify the equilibrium of the two conformational channel states that allow different modes of blockage. Our results suggest that the outward IK1 is primarily generated by channels with lower affinities for polyamines. Polyamines may regulate the amplitude of the outward IK1, not only by blocking the channels but also by modifying the proportion of channels that show different sensitivities to the polyamine block.
(Received 19 September 2003;
accepted after revision 6 January 2004;
first published online 14 January 2004)
Corresponding author K. Ishihara: Department of Physiology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan. Email: keiko{at}post.saga-med.ac.jp
This article has been cited by other articles:
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  B. K. Panama, M. McLerie, and A. N. Lopatin Heterogeneity of IK1 in the mouse heart Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3558 - H3567. [Abstract] [Full Text] [PDF]
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