Persistent calcium current in rat suprachiasmatic nucleus neurons

• Published in: Neuroscience 2006, Vol.138 (2), p.377-388
• Main Authors: Kononenko, N.I., Dudek, F.E.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; cadmium; Cadmium - pharmacology; Calcium Signaling - drug effects; Calcium Signaling - physiology; circadian rhythm; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Kinetics; Membrane Potentials; Neurons - drug effects; Neurons - physiology; nifedipine; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; SCN; spontaneous activity; Suprachiasmatic Nucleus - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2005.11.035

The suprachiasmatic nuclei contain the primary circadian clock, and suprachiasmatic nuclei neurons exhibit a diurnal modulation of spontaneous firing rate. The present study examined the voltage-gated persistent Ca 2+ current, in acutely isolated rat suprachiasmatic nuclei neurons using a ramp-type voltage-clamp protocol. Slow triangular voltage-clamp commands from a holding potential of −85 mV to +5 mV elicited inward current (100–400 pA) that was completely blocked by Cd 2+. This current showed little or no hysteresis, and was identified as persistent Ca 2+ current. The threshold for persistent Ca 2+ current ranged between −60 and −45 mV, and it was maximal at about −8 mV. Nifedipine at 10–20 μM blocked 80–100%. To assess the role of persistent Ca 2+ current in the generation of spontaneous action potentials in both acutely isolated and intact suprachiasmatic nuclei neurons, the effect of Cd 2+ and nifedipine on firing rate was studied using on-cell recording. Application of Cd 2+ exerted a weak excitatory effect and nifedipine had no significant effect on the spontaneous firing rate of isolated suprachiasmatic nuclei neurons. In all intact suprachiasmatic nuclei neurons in slice preparations ( n=15), Cd 2+ slowly inhibited spontaneous firing; in high-frequency firing cells (four of 15), a transient increase of firing rate preceded inhibition. No significant effect of nifedipine on firing rate of intact suprachiasmatic nuclei neurons was found. Therefore, persistent Ca 2+ current itself (as carrier of charge) does not appear to contribute significantly to spontaneous firing of suprachiasmatic nuclei neurons. A slowly developing inhibitory effect of Cd 2+ on spontaneous firing of intact suprachiasmatic nuclei neurons in slice preparations may be due to penetration of Cd 2+ through Ca 2+ channels, and its subsequent effect on intracellular mechanisms, while the transient increase of firing rate in high-frequency firing neurons is probably due to inhibition of Ca 2+-activated K + current.