Inhibition of Ca2+-activated large-conductance K+ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells

Liu Y, Savtchouk I, Acharjee S, Liu SJ. Inhibition of Ca2+ activated large-conductance K+ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells. J Neurophysiol 106: 144-152, 2011. First published May 11, 2011; doi:10.1152/jn.01107.2010.-Many fast-spiking inhibitory interneurons, including cerebellar stellate cells, fire brief action potentials and express alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)type glutamate receptors (AMPAR) that are permeable to Ca2+ and do not contain the GluR2 subunit. In a recent study, we found that increasing action potential duration promotes GluR2 gene transcription in stellate cells. We have now tested the prediction that activation of potassium channels that control the duration of action potentials can suppress the expression of GluR2-containing AMPARs at stellate cell synapses. We find that large-conductance Ca2+-activated potassium (BK) channels mediate a large proportion of the depolarization-evoked noninactivating potassium current in stellate cells. Pharmacological blockade of BK channels prolonged the action potential duration in postsynaptic stellate cells and altered synaptic AMPAR subtype from GluR2-lacking to GluR2-containing Ca2+-impermeable AMPARs. An L-type channel blocker abolished an increase in Ca2+ entry that was associated with spike broadening and also prevented the BK channel blocker-induced switch in AMPAR phenotype. Thus blocking BK potassium channels prolongs the action potential duration and increases the expression of GluR2-containing receptors at the synapse by enhancing Ca2+ entry in cerebellar stellate cells.