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pubmed:abstractText |
Cerebellar granule neurons express a standing outward (background) K+ current (I(K,SO)) that regulates the resting membrane potential and cell excitability. As several tandem-pore (2P) K+ channel mRNAs are highly expressed in cerebellar granule cells, we studied whether, and which, 2P K+ channels contribute to I(K,SO). I(K,SO) 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+ channels were found to be active when membrane potential was held at -50 mV or +50 mV in symmetrical 140 mM KCl. Based on single-channel conductances, gating kinetics and modulation by pharmacological agents and pH, three K+ channels could be considered as functional correlates of TASK-1, TASK-3 and TREK-2, which are members of the 2P K+ channel family. The fourth K+ 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+ channels were determined to be the major sources of I(K,SO) 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+ 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+ channels and an additional pH-sensing K+ channel (Type 4) comprise the I(K,SO) in cultured cerebellar granule neurons. Our results also show that the high sensitivity of I(K,SO) to extracellular pH comes from the high sensitivity of Type 2 (TASK-3) and Type 4 K+ channels.
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