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Biophysical Journal 84:2969-2980 (2003)
© 2003 The Biophysical Society

Stimulatory Action of Internal Protons on Slo1 BK Channels

Vladimir Avdonin *, Xiang Dong Tang {dagger} and Toshinori Hoshi {dagger}

* Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City, Iowa 52242; and {dagger} Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Correspondence: Address reprint requests to Toshinori Hoshi, Dept. of Physiology, Richards D100, 3700 Hamilton Walk, University of Pennsylvania, Philadelphia, PA 19104. Tel.: 215-573-7305; Fax: 215-573-5851; E-mail: hoshi{at}hoshi.org.

We investigated the internal pH-sensitivity of heterologously expressed hSlo1 BK channels. In the virtual absence of Ca2+ and Mg2+ to isolate the voltage-dependent gating transitions, low internal pH enhanced macroscopic hSlo1 currents by shifting the voltage-dependence of activation to more negative voltages. The activation time course was faster and the deactivation time course was slower with low pH. The estimated Kd value of the stimulatory effect was approximately pH = 6.5 or 0.35 µM. The stimulatory effect was maintained when the auxiliary subunit mouse ß1 was coexpressed. Treatment of the hSlo1 channel with the histidine modifying agent diethyl pyrocarbonate also enhanced the hSlo1 currents and greatly diminished the internal pH sensitivity, suggesting that diethyl pyrocarbonate and low pH may work on the same effector mechanism. High concentrations of Ca2+ or Mg2+ also masked the stimulatory effect of low internal pH. These results indicate that the acid-sensitivity of the Slo BK channel may involve the channel domain implicated in the divalent-dependent activation.




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