CAMP-DEPENDENT INWARD RECTIFIER CURRENT IN NEURONS OF THE RAT SUPRACHIASMATIC NUCLEUS

Electrophysiological properties of the inward rectification of neurons in the rat suprachiasmatic nucleus (SCN) were examined by using the single-electrode voltage-clamp method, in vitro. Inward rectifier current (I-H) was produced by hyperpolarizing step command potentials to membrane potentials negative to approximately -60 mV in nominally zero-Ca2+ Krebs solution containing tetrodotoxin (1 mu M), tetraethylammonium (40 mM), Cd2+ (500 mu M) and 4-aminopyridine (1 mM). I-H developed during the hyperpolarizing step command potential with a duration of up to 5 s showing no inactivation with time. I-H was selectively blocked by extracellular Cs+ (1 mM). The activation of the H-channel conductance (G(H)) ranged between -55 and -120 mV. The G(H) was 80-150 pS (n=4) at the half-activation voltage of -84+/-7 mV (n=4). The reversal potential of I-H obtained by instantaneous current voltage (I/V) relations was -41+/-6 mV (n=4); it shifted to -51+/-8 mV (n=3) in low-Na+ (20 mM) solution and to -24+/-4 mV (n=4) in high-K+ (20 mM) solution. Forskolin (1-10 mu M) produced an inward current and increased the amplitude of I-H. Forskolin did not change the half-activation voltage of G(H). 8-Bromo-adenosine 3',5'-cyclic monophosphate (8-Br-cAMP, 0.1-1 mM) and dibutyryl-cAMP (0.1-1 mM) enhanced I-H. 3-Isobutyl-1-methylxanthine (IBMX, 1 mM) also enhanced I-H. The results suggest that the inward rectifier cation current is regulated by the basal activity of adenylate cyclase in neurons of the rat SCN.