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Science Signaling  04 Mar 2008:
Vol. 1, Issue 9, pp. ec78
DOI: 10.1126/stke.19ec78

Petroff et al. describe an interaction between two ion channels that confers sensitivity of K+ channels to extracellular protons. The authors studied acid-sensing ion channels (ASICs), which are Na+-conducting neuronal channels whose conductance is increased by reduced extracellular pH. These channels are implicated in regulation of a range of physiologic and pathological processes. Their Na+ conductance would tend to depolarize neurons, but some of their actions in mice are not easily explained by such a mechanism. In searching for another mechanism by which ASICs might function, the authors noted that the channels contain a conserved sequence similar to the portion of scorpion alpha-K-toxins that plugs the pore of K+ channels, inhibiting their conductance. Indeed, when ASIC1a channels were expressed together with high-conductance Ca2+- and voltage-activated (BK) K+ channels in human embryonic kidney (HEK) 293 cells, current flow through the BK channels was reduced. The proteins appeared to interact with one another as they promoted interaction of fluorescently tagged cells expressing one or the other of the channels. Addition of protons inhibited clustering and relieved the inhibition of the BK channel conductance. The function of the ASIC1a channels was also modified by the interaction, showing reduced current amplitude and an increased time for desensitization. Thus, interaction of two unrelated channels alters the activity of the channels and confers sensitivity to acidosis on BK channels. Acidosis occurs with neuronal activity in various pathological states and through this mechanism would modulate channel function and produce opposing effects on membrane voltage through the ASIC and BK channels.

E. Y. Petroff, M. P. Price, V. Snitsarev, H. Gong, V. Korovkina, F. M. Abboud, M. J. Welsh, Acid-sensing ion channels interact with and inhibit BK K+ channels. Proc. Natl. Acad. Sci. U.S.A. 105, 3140-3144 (2008). [Abstract] [Full Text]

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