抄録
The outward current of the strong inward rectifier K+ currents (IKIR) plays an important role in hyperpolarizing the membrane potential in many types of excitable and non-excitable cells. The detailed mechanism of outward IKIR has not been well understood, because the time-dependent gating mechanism reflecting the block and unblock of the channels by intracellular spermine maximally "closes" the channels at voltages where outward IKIR flows. In our previous study on the Kir2.1 channel, which is considered to be the predominant channel contributing to IKIR, we showed that high-affinity block by spermine causes the time-dependent gating, but that the channels mediating ∼10% of the maximum conductance show lower sensitivity to the spermine block and the outward currents flow through these channels. In this study, we analyzed the Kir2.1 channels harboring mutations of the negatively charged residues on the wall of the pore, which are reportedly involved in the block by spermine. Neutralization of Asp174 in the transmembrane pore region made the channel susceptible only to the low-affinity spermine block, while that of Glu224 in the cytoplasmic pore region greatly reduced the sensitivity of the channel to the low-affinity spermine block without markedly altering the fractional conductance attributed to the low-affinity channels. These findings support our view that there are two populations of Kir2.1 channels susceptible to different modes of spermine block. [J Physiol Sci. 2007;57 Suppl:S226]
