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 (K-ir) and high voltage-activated calcium currents (I-Ca). In cells expressing CB-1 (''A-2'' cells), cannabinoid agonist potently and stereospecifically activated K-ir via a pertussis toxin-s ensitive G protein. I-Ca in A-2 cells was sensitive to dihydropyridine s and omega CTX MVIIC, less so to omega CgTX GVIA and insensitive to o mega Aga IVa. In CB-1-expressing cells, cannabinoid agonist inhibited only the omega CTX MVIIC-sensitive component of I-Ca. Inhibition of Q- type I-Ca was voltage dependent and PTX sensitive, thus similar in cha racter to the well-studied modulation of N-type I-Ca. An endogenous ca nnabinoid, anandamide, activated K-ir and inhibited I-Ca as efficaciou sly as potent cannabinoid agonist. Immunocytochemical studies with ant ibodies 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.