The effect of metabotropic glutamate receptor activation on Ca dihydropyridine (DHP)-sensitive channels recorded in the presence of 1 PM Bay K 8844 was examined on cultured cerebellar granule cells using the patch-clamp technique in the ceil-attached configuration. Bath-applied agonist (frans-ACPD, 1 S,3R-, and 1 R,3SACPD isomers, and glutamate or quisqualate in the presence of CPP and CNQX) evoked an increase in Ca channel activity with a variable latency of 8.9 + 8.8 set in 40% of the recorded cells. Neither L-CCGl, L-AP3, L-AP4, nor AMPA or NMDA activated Ca channels. Two dihydropyridine-sensitive channels present in this cell type were activated by frans-ACPD: the classical 24 pS L-type channel and a smaller-conductance 7 pS channel. The effect was shown to be mediated by neither intracellular Ca*+ nor a pertussis toxin (PTX)-sensitive G protein. Interestingly treatment with BAPTA-AM increased the number of responding patches and the activity was more sustained throughout the drug application.After overnight PTX treatment, activation of the Ca channels persisted even after washout of the agonist. These results indicate that mGluRl/mGluRB probably mediate the facilitation of dihydropyridine-sensitive Ca channels.[Key words: Cb+ current, glutamate metaborropic receptor, Ca channel facilitation, cerebellum, G protein, patch clamp]Glutamate is a major neurotransmitter in the mammalian CNS. It activates two families of receptors, the ionotropic (AMPA, kainate, and NMDA) and the metabotropic glutamate receptors (mGluRs). Among the metabotropic receptor family, six receptor subtypes have been cloned (Houamed et al., 199 1; Masu et al., 199 1;Tanabe et al., 1992) and their pharmacology and coupling mechanisms characterized (Schoepp et al., 1990; Schoepp and Corm, 1993). The mGluR 1 and mGluR5 subtypes are positively coupled to phospholipase C and lead to inositol
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