On the role of calcium and potassium currents in circadian modulation of firing rate in rat suprachiasmatic nucleus neurons: Multielectrode dish analysis

The master circadian clock of mammals in the suprachiasmatic nucleus (SCN) of the hypothalamus entrains to a 24-h daily light-dark cycle and regulates circadian rhythms. The SCN is composed of multiple neurons with cell autonomous clocks exhibiting robust firing rhythms with a high firing rate during the subjective day. The membrane target(s) of the cellular clock responsible for circadian modulation of the firing rate in SCN neurons still remain unclear. Previously, L-type Ca2+ currents and fast delayed rectifier (FDR) K+ currents have been suggested to contribute directly to circadian modulation of electrical activity. Using long-term continuous recording of activity from dispersed rat SCN neurons in multielectrode dish and ionic channel blockers, we tested these hypotheses. Neither an L-type Ca2+ current blocker (20 μM of nifedipine for 2 days) nor an FDR current blocker (500 μM of 4-aminopyridine (4-AP) for 4 days) suppressed the circadian modulation of firing rate. A specific blocker of Na+ persistent current (5 μM of riluzole for 1 day followed by 10 μM during the next day) reversibly suppressed firing activity in a dose-dependent manner. These data indicate that neither nifedipine-sensitive Ca2+ current(s) nor 4-AP-sensitive K+ current(s) are key membrane targets for circadian modulation of electrical firing rate in SCN neurons.