Modulation of big K+ channel activity by ryanodine receptors and L-type Ca2+ channels in neurons.
As metabotropic glutamate receptor type 1 (mGluR1) is known to couple L-type Ca2+ channels and ryanodine receptors (RyR, Chavis et al., 1996) 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)-alpha-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.
Chavis
P
P
CNRS UPR 9023, Montpellier, France.
Ango
F
F
Michel
J M
JM
Bockaert
J
J
Fagni
L
L
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D020746:Calcium Channels, L-Type; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D015221:Potassium Channels; D018094:Receptors, Metabotropic Glutamate; D011976:Receptors, Muscarinic; D019837:Ryanodine Receptor Calcium Release Channel