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Ryanodine-Sensitive Intracellular Ca²⁺ Channels in Rat Suprachiasmatic Nuclei Are Required for Circadian Clock Control of Behavior

Departamento de Neurociencias, Instituto de Fisiología Celular, Distrito Federal, México, Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Querétaro, México, Universidad Nacional Autónoma de México

Mauricio Díaz-Muñoz

Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Querétaro, México, Universidad Nacional Autónoma de México

Javier Alamilla

Departamento de Neurociencias, Instituto de Fisiología Celular, Distrito Federal, México

Karla Valderrama

Departamento de Neurociencias, Instituto de Fisiología Celular, Distrito Federal, México

Verónica Morales-Tlalpan

Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Querétaro, México, Universidad Nacional Autónoma de México

Raúl Aguilar-Roblero

Departamento de Neurociencias, Instituto de Fisiología Celular, Distrito Federal, México, raguilar{at}ifc.unam.mx

Electrophysiological and calcium mobilization experiments have suggested that the intracellular calcium release channel ryanodine receptors (RyRs) are involved in the circadian rhythmicity of the suprachiasmatic nucleus (SCN). In the present report the authors provide behavioral evidence that RyRs play a specific and major role in the output of the molecular circadian clock in SCN neurons. They measured the circadian rhythm of drinking and locomotor behaviors in dim red light before, during, and after administration of an activator (ryanodine 0.1 µM) or an inhibitor (ryanodine 100 µM) of the RyRs. Drugs were delivered directly into the SCN by cannulas connected to osmotic minipumps. Control treatments included administration of artificial cerebrospinal fluid, KCl (20 mM), tetrodotoxin (1 µM), and anysomicin (5 µg/µl). Activation of RyRs induced a significant shortening of the endogenous period, whereas inhibition of these Ca²⁺ release channels disrupted the circadian rhythmicity. After the pharmacological treatments the period of rhythmicity returned to basal values and the phase of activity onset was predicted from a line projected from the activity onset of basal recordings. These results indicate that changes in overt rhythms induced by both doses of ryanodine did not involve an alteration in the clock mechanism. The authors conclude that circadian modulation of RyRs is a key element of the output pathway from the molecular circadian clock in SCN neurons in rats.

Key Words: circadian timing system • suprachiasmatic nucleus • ryanodine receptor • intracellular calcium • circadian output • behavioral regulation

Journal of Biological Rhythms, Vol. 24, No. 3, 203-210 (2009)
DOI: 10.1177/0748730409333354


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