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Searching of a membrane target for mammalian circadian clock responsible for circadian modulation of firing rate Nikolai I. Kononenko Department of General Physiology of Nervous System, Bogomoletz Institute of Physiology, Kiev, Ukraine
1. The suprachiasmatic nucleus (SCN) of the hypothalamus is the primary biological clock regulating circadian rhythms in mammals
2. Individual SCN neurons express self-sustained circadian oscillations. As a result of internal coupling, the SCN generates a coherent output signal
Spike-associated currents are key targets for circadian modulation of firing rate First of all, we asked whether spike-associated currents (i.e., currents active only during action potentials) are indeed primary membrane target(s) responsible for circadian modulation of firing rate (CMFR).
B A Action potentials across the circadian cycle Thus, result allowed preliminarily to suggest that spike-associated currents are not a key targets for circadian modulation of firing rate.
Effect of 4-aminopyridine on circadian rhythms of firing rate in SCN neurons
A B Cd 2+ does not suppress immediately spontaneous activity and its circadian modulation (n=13 neurons)
Spike-associated channels are not the principal determinants of circadian modulation of firing rate
Two acutely isolated SCN neurons on the bottom of a Petri dish 6 days after isolation 100 m
On-cell recording of single channels 2 pA 100 ms
Spontaneous firing of isolated SCN neurons and circadian modulation of their firing rate Noon Midnight Noon of the next day
2 s (A) 5 s (B) 7 pA 20 mV A B 0 pA C V h = -90 mV V h = -65 mV 2 s 5 pA Fluctuation of membrane potential produces spontaneous activity of SCN neuron
The numerous single-channel inward currents we observed during on-cell recording of spontaneous electrical firing in isolated SCN neurons led us to study the properties of the corresponding channels in their relation to spontaneous electrical firing
The present findings bring together several lines of study seeking a membrane target of the circadian clock, and bridge the gap between single-channel physiology and features of circadian rhythms of firing rate.
The SVC single channels described here are proposed to be a key membrane target mediating the effects of circadian clock protein concentration on electrical firing rate.
Concomitantly, these data delineate a novel pathway that links the core circadian clock with membrane events regulating spontaneous firing in SCN neurons.
Acknowledgments: The author thanks Dr. F.E. Dudek (University of Utah School of Medicine, Salt Lake City, USA) and Dr. S. Honma (Hokkaido University Graduate School of Medicine, Sapporo, Japan), in whose laboratories experimental data were obtained, and Dr. N.M. Berezetskaya (Institute of Physics, Kiev, Ukraine), who converted differential equations into computer programs.