Cannabinoids activate an inwardly rectifying potassium conductance and inhibit Q-type calcium currents in AtT20 cells transfected with rat brain cannabinoid receptor

Abstract

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-sensitive G protein. I(Ca) in A-2 cells was sensitive to dihydropyridines and ωCTX MVIIC, less so to ωCgTX GVIA and insensitive to ωAga IVa. In CB-1- expressing cells, cannabinoid agonist inhibited only the ωCTX MVIIC- sensitive component of I(Ca). Inhibition of Q-type I(Ca) was voltage dependent and PTX sensitive, thus similar in character to the well-studied modulation of N-type I(Ca). An endogenous cannabinoid, anandamide, activated K(ir) and inhibited I(Ca) as efficaciously as potent cannabinoid agonist. Immunocytochemical studies with antibodies specific for class A, B, C, D, and E voltage-dependent calcium channel α1 subunits revealed that ART-20 cells express each of these major classes of α1 subunit.