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The selectivity, voltage-dependence and acid sensitivity of the tandem pore potassium channel TASK-1 : contributions of the pore domains

By K. H. Yuill, P. J. Stansfeld, I. Ashmole, M. J. Sutcliffe and Peter R. Stanfield


We have investigated the contribution to ionic\ud selectivity of residues in the selectivity filter and pore\ud helices of the P1 and P2 domains in the acid sensitive\ud potassium channel TASK-1. We used site directed mutagenesis\ud and electrophysiological studies, assisted by structural\ud models built through computational methods. We have\ud measured selectivity in channels expressed in Xenopus\ud oocytes, using voltage clamp to measure shifts in reversal\ud potential and current amplitudes when Rb+ or Na+ replaced\ud extracellular K+. Both P1 and P2 contribute to selectivity,\ud and most mutations, including mutation of residues in the\ud triplets GYG and GFG in P1 and P2, made channels nonselective.\ud We interpret the effects of these—and of other\ud mutations—in terms of the way the pore is likely to be\ud stabilised structurally. We show also that residues in the\ud outer pore mouth contribute to selectivity in TASK-1.\ud Mutations resulting in loss of selectivity (e.g. I94S, G95A)\ud were associated with slowing of the response of channels to\ud depolarisation. More important physiologically, pH sensitivity\ud is also lost or altered by such mutations. Mutations\ud that retained selectivity (e.g. I94L, I94V) also retained their\ud response to acidification. It is likely that responses both to\ud voltage and pH changes involve gating at the selectivity filter

Topics: QP
Publisher: Springer
Year: 2007
OAI identifier:

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