G alpha q/11 mediates cholecystokinin activation of the cationic conductance in rat substantia nigra dopaminergic neurons.
Using acutely isolated rat substantia nigra neurons, our previous studies indicated that sulfated cholecystokinin octapeptide (CCK-8) excites substantia nigra dopaminergic neurons by increasing the cationic conductance and that pertussis toxin-insensitive G proteins mediate CCK-8 induction of cationic currents. G alpha q and G alpha 11 are expressed in various tissues, including the brain, and likely to mediate pertussis toxin-insensitive neural signal transductions. In the present study, two different experiments were performed to test the hypothesis that G alpha q/11 mediates CCK-8 enhancement of the cationic conductance. First, we investigated the expression of G alpha q and G alpha 11 mRNAs in CCK-8-responsive substantia nigra dopaminergic neurons by combining whole-cell patch-clamp recordings with a single-cell reverse transcriptase-polymerase chain reaction assay. After CCK-8-evoked cationic currents were recorded, cellular RNA was harvested from single neurons and used as a template for the subsequent reverse transcriptase-polymerase chain reaction analysis. G alpha q and G alpha 11 mRNAs were present in all substantia nigra dopaminergic neurons that responded to CCK-8. Substantia nigra dopaminergic neurons were also internally perfused with the antibody raised against the common C-terminus of G alpha q and G alpha 11 during whole-cell recordings. CCK-8 failed to induce cationic currents after dopaminergic neurons were dialyzed with the anti-G alpha q/11 antibody. Our studies suggest that CCK-8 activation of the cationic conductance in substantia nigra dopaminergic neurons is transduced by G alpha q and/or G alpha 11.
Wu
T
T
Department of Neurology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, Republic of China.
Wang
H L
HL
D000818:Animals; D001483:Base Sequence; D002412:Cations; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007106:Immune Sera / Q000276:immunology; D007473:Ion Channels / Q000502:physiology*; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D015345:Oligonucleotide Probes / Q000235:genetics; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000494:pharmacology*; D013378:Substantia Nigra / Q000166:cytology / Q000502:physiology*
D002412:Cations; D007106:Immune Sera; D007473:Ion Channels; D015345:Oligonucleotide Probes; D010446:Peptide Fragments; D012333:RNA, Messenger; D019204:GTP-Binding Proteins; D012844:Sincalide; D004298:Dopamine