Characterization of four types of background potassium channels in rat cerebellar granule neurons

<jats:p>Cerebellar granule neurons express a standing outward (background) K<jats:sup>+</jats:sup> current (<jats:italic>I</jats:italic><jats:sub>K,SO</jats:sub>) that regulates the resting membrane potential and cell excitability. As several tandem‐pore (2P) K<jats:sup>+</jats:sup> channel mRNAs are highly expressed in cerebellar granule cells, we studied whether, and which, 2P K<jats:sup>+</jats:sup> channels contribute to <jats:italic>I</jats:italic><jats:sub>K,SO</jats:sub>. <jats:italic>I</jats:italic><jats:sub>K,SO</jats:sub> was highly sensitive to changes in extracellular pH and was partially inhibited by acetylcholine, as reported previously. In cell‐attached patches from cultured cerebellar granule neurons, four types of K<jats:sup>+</jats:sup> channels were found to be active when membrane potential was held at −50 mV or +50 mV in symmetrical 140 m<jats:sc>m</jats:sc>) KCl. Based on single‐channel conductances, gating kinetics and modulation by pharmacological agents and pH, three K<jats:sup>+</jats:sup> channels could be considered as functional correlates of TASK‐1, TASK‐3 and TREK‐2, which are members of the 2P K<jats:sup>+</jats:sup> channel family. The fourth K<jats:sup>+</jats:sup> channel (Type 4) has not been described previously and its molecular correlate is not yet known. Based on the measurement of channel current densities, the Type 2 (TASK‐3) and the Type 4 K<jats:sup>+</jats:sup> channels were determined to be the major sources of <jats:italic>I</jats:italic><jats:sub>K,SO</jats:sub> in cultured cerebellar granule neurons. The Type 1 (TASK‐1) and Type 3 (TREK‐2) activities were relatively low throughout cell growth in culture (1‐10 days). Similar to TASK‐1 and TASK‐3, the Type 4 K<jats:sup>+</jats:sup> channel was highly sensitive to changes in extracellular pH, showing a 78 % inhibition by changing the extracellular pH from 7.3 to 6.3. The results of this study show that three 2P K<jats:sup>+</jats:sup> channels and an additional pH‐sensing K<jats:sup>+</jats:sup> channel (Type 4) comprise the <jats:italic>I</jats:italic><jats:sub>K,SO</jats:sub> in cultured cerebellar granule neurons. Our results also show that the high sensitivity of <jats:italic>I</jats:italic><jats:sub>K,SO</jats:sub> to extracellular pH comes from the high sensitivity of Type 2 (TASK‐3) and Type 4 K<jats:sup>+</jats:sup> channels.</jats:p>