Abstract
The outward current of IK1 shows significant amplitude in the voltage range near the reversal potential and thereby causes rapid repolarization at the final phase of action potentials. However, the mechanism that produces the outward IK1 is not understood. The currents generated by expressing the strong inward rectifier K+ channel gene Kir2.1 resemble IK1 under the whole-cell recordings. In this study, we recorded currents from inside-out patches of 293T cells that express Kir2.1 and studied the blockage of the currents by cytoplasmic polyamines. The outward current-voltage relationships, obtained with 5-10 μM spermine (spm) or 10-100 μM spermidine (spd), were similar to that of IK1, while they exhibited a plateau or a double-hump shape at lower spm/spd concentrations. There were extra conductances in the chord conductance-voltage relationships, which could not be described by the Boltzmann relations fitting the major part of the relationships. The extra conductances were quantitatively explained by a model that considered two populations of channels, which were blocked by polyamines in either a high-affinity mode (Mode 1 channel) or a low-affinity mode (Mode 2 channel). The estimated proportion of Mode 1 to total channels was 0.9 with 0.1-10 μM spm and between 0.75 and 0.9 when spm and spd coexisted. Our results suggest that the outward current of IK1 is primarily generated by the Mode 2 channels. Polyamines may regulate IK1, not only by blocking the channels but also by modifying the proportion of channels that show different sensitivities to the polyamine block. [Jpn J Physiol 54 Suppl:S102 (2004)]
