Stimulatory Action of Internal Protons on Slo1 BK Channels

Abstract

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.

Acid-sensing ion channels interact with and inhibit BK K + channels

“…Although ASIC1a can conduct H ϩ , the stimulating effect of intracellular H ϩ on BK channels has been observed only in the absence of divalent cations (29), and in our experiments the intracellular solution contained 4.8 mM Mg 2ϩ . In addition, dropping pH to values Ͻ6 elicited no additional relief of BK inhibition by ASIC1a (Fig.…”

Mechanism of Proton Gating of a Urea Channel

“…For the acid-sensing ion channels, extracellular protons enhance the release of Ca 2ϩ , enabling ion conduction (25). In the voltage-sensitive ROMK channel (Kir1.1) and the Slo1-BK channel, intracellular protons modify local surface potential, thereby shifting the voltage dependence of activation (21,22). pH-sensitive transport of a neutral solute has also been described in aquaporin 3 (AQP3) in which extracellular protons block transport by competing with glycerol for binding sites within the channel conduction pathway (26).…”

Ligand-Dependent Activation of Slo Family Channels Is Defined by Interchangeable Cytosolic Domains

“…In contrast, changes in pH from 7.0 to 8.0 have minor effects on Slo1 G-V curves either at 0 Ca 2ϩ or at 300 M Ca 2ϩ (Fig. 3B), with only a small enhancement at lower pH (Avdonin et al, 2003). For Slo3, increases in cytosolic pH from 7.0 to 8.0 result in marked activation of current (Schreiber et al, 1998) (Fig.…”