Cannabinoids activate an inwardly rectifying potassium conductance and inhibit Q-type calcium currents in AtT20 cells transfected with rat brain cannabinoid receptor.
Rat brain cannabinoid receptor (CB-1) was stably transfected into the murine tumor line AtT-20 to study its coupling to inwardly rectifying potassium currents (Kir) and high voltage-activated calcium currents (ICa). In cells expressing CB-1 ("A-2" cells), cannabinoid agonist potently and stereospecifically activated Kir via a pertussis toxin-sensitive G protein. ICa in A-2 cells was sensitive to dihydropyridines and omega CTX MVIIC, less so to omega CgTX GVIA and insensitive to omega Aga IVa. In CB-1 expressing cells, cannabinoid agonist inhibited only the omega CTX MVIIC-sensitive component of ICa. Inhibition of Q-type ICa was voltage dependent and PTX sensitive, thus similar in character to the well-studied modulation of N-type ICa. An endogenous cannabinoid, anandamide, activated Kir and inhibited ICa as efficaciously as potent cannabinoid agonist. Immunocytochemical studies with antibodies specific for class A, B, C, D, and E voltage-dependent calcium channel alpha 1 subunits revealed that AtT-20 cells express each of these major classes of alpha 1 subunit.
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology; D002186:Cannabinoids / Q000494:pharmacology*; D002460:Cell Line; D004553:Electric Conductivity; D007150:Immunohistochemistry; D051379:Mice; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D011188:Potassium / Q000502:physiology*; D051381:Rats; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002186:Cannabinoids; D015335:Molecular Probes; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D011188:Potassium; D002118:Calcium