Mechanism of Spontaneous Firing in Dorsomedial Suprachiasmatic Nucleus Neurons

Abstract

We studied acutely dissociated neurons from the dorsomedial (shell) region of the rat suprachiasmatic nucleus (SCN) with the aim of determining the ionic conductances that underlie spontaneous firing. Most isolated neurons were spontaneously active, firing rhythmically at an average frequency of 8 Ϯ 4 Hz. After application of TTX, oscillatory activity generally continued, but more slowly and at more depolarized voltages; these oscillations were usually blocked by 2 M nimodipine. To quantify the ionic currents underlying normal spontaneous activity, we voltage clamped cells using a segment of the spontaneous activity of each cell as voltage command and then used ionic substitution and selective blockers to isolate individual currents. TTX-sensitive sodium current flowed throughout the interspike interval, averaging Ϫ3 pA at Ϫ60 mV and Ϫ11 pA at Ϫ55 mV. Calcium current during the interspike interval was, on average, fourfold smaller. Except immediately before spikes, calcium current was outweighed by calcium-activated potassium current, and in current clamp, nimodipine usually depolarized cells and slowed firing only slightly (average, ϳ8%). Thus, calcium current plays only a minor role in pacemaking of dissociated SCN neurons, although it can drive oscillatory activity with TTX present. During normal pacemaking, the early phase of spontaneous depolarization (Ϫ85 to Ϫ60 mV) is attributable mainly to background conductance; cells have relatively depolarized resting potentials (with firing stopped by TTX and nimodipine) of Ϫ55 to Ϫ50 mV, although input resistance is high (9.5 Ϯ 4.1 G⍀). During the later phase of pacemaking (positive to Ϫ60 mV), TTX-sensitive sodium current is dominant.

The expression of L‐type voltage‐gated calcium channels in retinal photoreceptors is under circadian control

“…However, it is controversial as to the precise physiological role of this rhythm in suprachiasmatic nucleus neurons (Pennartz et al 2002;Cloues and Sather 2003;Jackson et al 2004). One possibility is that L-type VGCCs could participate in the circadian input pathway to synchronize the rhythmicity of the expression of clock genes such as Per2 and Bmal1 (Nahm et al 2005).…”

CaV1.3 as pacemaker channels in adrenal chromaffin cells: Specific role on exo- and endocytosis?

“…46 In MCCs and RCCs this is not always the case, in some cells the block of firing by Cd 2+ causes slight depolarizations, as illustrated in Figure 2, indicating a parallel block of Ca 2+ -activated K + currents. As in SNc [46][47][48][49][50] and other neurons, [51][52][53][54][55][56] the persisting firing in the presence of TTX can be effectively blocked by nifedipine (3 μM) and accelerated by BayK 8644 (1 μM) (Fig. 2, bottom), suggesting a main role of LTCCs in controlling AP firing in these cells.…”

L-type channel inhibition by CB1 cannabinoid receptors is mediated by PTX-sensitive G proteins and cAMP/PKA in GT1-7 hypothalamic neurons

“…As LTCCs are mainly expressed in the soma and proximal dendrites of neurons and abundantly in neuroendocrine cells, their inhibition by CB1R most likely will alter somatic activities and hormone release. For instance, LTCCs activating at subthreshold potentials are expressed in midbrain dopaminergic neurons of substantia nigra [57] and hypothalamic suprachiasmatic nucleus neurons [58], which also express high densities of CB1R [59]. LTCCs regulate the shape of action potentials and the frequency of spontaneous firing [60], thus an effective up-or down-modulation of these channels by CB1R activation or deactivation can cause drastic changes to neuronal firing, neurotransmitter release and brain functions control.…”