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Synergistic inhibition of the maximum conductance of Kv1.5 channels by extracellular K+ reduction and acidification

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Abstract

Voltage-gated potassium (Kv) channels exist in the membranes of all living cells. Of the functional classes of Kv channels, the Kv1 channels are the largest and the best studies and are known to play essential roles in excitable cell function, providing an essential counterpoin to the various inward currents that trigger excitability. The serum potassium concentration [K +o ] is tightly regulated in mammals and disturbances can cause significant functional alterations in the electrical behavior of excitable tissues in the nervous system and the heart. At least some of these changes may be mediated by Kv channels that are regulated by changes in the extracellular K+ concentration. As well as changes in serum [K +o ], tissue acification is a frequent pathological condition known to inhibit Shaker and Kv1 voltage-gated potassium channels. In recent studies, it has become recognized that the acidification-induced inhibition of some Kv1 channels is K +o -dependent, and the suggestion has been made that pH and K +o may regulate the channels via a common mechanism. Here we discuss P/C type inactivation as the common pathway by which some Kv channels become unavailable at acid pH and lowered K +o . It is suggested that binding of protons to a regulatory site in the outer pore mouth of some Kv channels favors transitions to the inactivated state, whereas K+ ions exert countereffects. We suggest that modulation of the number of excitable voltage-gated K+ channels in the open vs inactivated states of the channels by physiological H+ and K+ concentrations represents an important pathway to control Kv channel function in health and disease.

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  1. Department of Physiology, University of British Columbia, 2146 Health Sciences Mall, V6T 1Z3, Vancouver, British Columbia, Canada

    David Fedida, Daniel C. H. Kwan, Cyrus Eduljee & Steven J. Kehl

  2. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Center, University of Manitoba, 351 Tache Avenue, R2H 2A6, Winnipeg, Manitoba, Canada

    Shetuan Zhang

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  1. David Fedida
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Correspondence to David Fedida.

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Fedida, D., Zhang, S., Kwan, D.C.H. et al. Synergistic inhibition of the maximum conductance of Kv1.5 channels by extracellular K+ reduction and acidification. Cell Biochem Biophys 43, 231–242 (2005). https://doi.org/10.1385/CBB:43:2:231

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