HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental data All Versions of this Article: 583/3/891    most recent jphysiol.2007.136028v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ishihara, K. Articles by Yan, D.-H. Search for Related Content PubMed PubMed Citation Articles by Ishihara, K. Articles by Yan, D.-H. Related Collections Molecular and Genomic

¹ Department of Physiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan

The outward component of the strong inward rectifier K⁺ current (I_Kir) plays a pivotal role in polarizing the membranes of excitable and non-excitable cells and is regulated by voltage-dependent channel block by internal cations. Using the Kir2.1 channel, we previously showed that a small fraction of the conductance susceptible only to a low-affinity mode of block likely carries a large portion of the outward current. To further examine the relevance of the low-affinity block to outward I_Kir and to explore its molecular mechanism, we studied the block of the Kir2.1 and Kir2.2 channels by spermine, which is the principal Kir2 channel blocker. Current–voltage relations of outward Kir2.2 currents showed a peak, a plateau and two peaks in the presence of 10, 1 and 0.1 µM spermine, respectively, which was explained by the presence of two conductances that differ in their susceptibility to spermine block. When the current–voltage relations showed one peak, like those of native I_Kir, outward Kir2.2 currents were mediated mostly by the conductance susceptible to the low-affinity block. They also flowed in a narrower range than the corresponding Kir2.1 currents, because of 3- to 4-fold greater susceptibility to the low-affinity block than in Kir2.1. Reducing external [K⁺] shifted the voltage dependences of both the high- and low-affinity block of Kir2.1 in parallel with the shift in the reversal potential, confirming the importance of the low-affinity block in mediating outward I_Kir. When Kir2.1 mutants known to have reduced sensitivity to internal blockers were examined, the D172N mutation in the transmembrane pore region made almost all of the conductance susceptible only to low-affinity block, while the E224G mutation in the cytoplasmic pore region reduced the sensitivity to low-affinity block without markedly altering that to the high-affinity block or the high/low conductance ratio. The effects of these mutations support the hypothesis that Kir2 channels exist in two states having different susceptibilities to internal cationic blockers.

(Received 11 May 2007; accepted after revision 13 July 2007; first published online 19 July 2007)
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:

				M. Hassinen, V. Paajanen, and M. Vornanen A novel inwardly rectifying K+ channel, Kir2.5, is upregulated under chronic cold stress in fish cardiac myocytes J. Exp. Biol., July 1, 2008; 211(13): 2162 - 2171. [Abstract] [Full Text] [PDF]