Modulation of big K+ channel activity by ryanodine receptors and L‐type Ca2+ channels in neurons

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Abstract
As metabotropic glutamate receptor type 1 (mGluR1) is known to couple L‐type Ca2+ channels and ryanodine receptors (RyR, 1 ) in cerebellar granule cells, we examined if such a coupling could activate a Ca2+‐sensitive K+ channel, the big K+ (BK) channel, in cultured cerebellar granule cells. We observed that (±)‐1‐amino‐cyclopentane‐trans‐1,3‐dicarboxylic acid (t‐ACPD) and quisqualate (QA) stimulated the activity of BK channels. On the other hand, (2S, 3S, 4S)‐α‐carboxycyclopropyl‐glycine (L‐CCG‐I) and l‐(+)‐2‐amino‐4‐phosphonobutyrate (L‐AP4) had no effect on BK channels, indicating a specific activation by group I mGluRs. Group I mGluRs stimulation of the basal BK channel activity was mimicked by caffeine and both effects were blocked by ryanodine and nifedipine. Interestingly, carbachol stimulated BK channel activity but through a pertussis toxin (PTX)‐sensitive pathway that was independent of L‐type Ca2+ channel activity. Our report indicates that unlike the muscarinic receptors, group I mGluRs activate BK channels by mobilizing an additional pathway involving RyR and L‐type Ca2+ channels.