Stimulatory action of internal protons on Slo1 BK channels.
We investigated the internal pH-sensitivity of heterologously expressed hSlo1 BK channels. In the virtual absence of Ca(2+) and Mg(2+) 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 K(d) value of the stimulatory effect was approximately pH = 6.5 or 0.35 micro M. The stimulatory effect was maintained when the auxiliary subunit mouse beta1 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 Ca(2+) or Mg(2+) 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.
Avdonin
Vladimir
V
Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City 52242, USA.
Tang
Xiang Dong
XD
Hoshi
Toshinori
T
D000818:Animals; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007668:Kidney / Q000187:drug effects / Q000196:embryology / Q000502:physiology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008274:Magnesium / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011522:Protons; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D011522:Protons; D008274:Magnesium; D004047:Diethyl Pyrocarbonate; D002118:Calcium