Activation of melatonin receptor increases a delayed rectifier K + current in rat cerebellar granule cells

• Published in: Brain research Vol. 917; no. 2; pp. 182 - 190
• Main Authors: Huan, Chun-lei, Zhou, Mi-ou, Wu, Ming-ming, Zhang, Zhi-hong, Mei, Yan-ai
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 02.11.2001; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Biological and medical sciences; Cells, Cultured; Central nervous system; Cerebellar granule cell; Cerebellum - cytology; Cerebellum - metabolism; Delayed Rectifier Potassium Channels; Electric Conductivity; Electrophysiology; Fundamental and applied biological sciences. Psychology; GTP-Binding Proteins - metabolism; K + current; Melatonin - pharmacology; Melatonin receptor; Potassium Channels - drug effects; Potassium Channels - physiology; Potassium Channels, Voltage-Gated; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface - physiology; Receptors, Cytoplasmic and Nuclear - physiology; Receptors, Melatonin; Vertebrates: nervous system and sense organs; K + current; Excitable membranes and synaptic transmission; Cerebellar granule cell; Melatonin receptor; Cerebellum; Melatonin; Granule neuron; Rat; Rodentia; Central nervous system; Electrophysiology; Patch clamp method; Ionic current; Vertebrata; Mammalia; Potassium; Brain (vertebrata); Pineal hormone
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(01)02915-8

The present study was initiated to investigate the effect of melatonin on K + current in rat cerebellar granule cells for 2 to 6 days in culture (DIC). The whole-cell configuration of the conventional patch-clamp technique was used to record the outward K + current. Two types of outward K + current, a transient outward K + current and a delayed rectifier K + current, were separated by different voltage protocols and a specific blocker of K + channel. Application of melatonin (10 μM) by a brief pressure ejection induced a significant and reversible increase of the delayed rectifier K + current amplitude in 78% of the cells tested. The activated effect of melatonin on the K + current was independent of the time in culture, and the percentage of activation remained at a relatively stable level from 2 DIC to 6 DIC; but that was dependent on the concentration of melatonin applied. The activation of the K + current induced by melatonin presented no desensitization after repeated application of melatonin. The effect of melatonin on the K + current can be mimicked by 2-iodomelatonin, a melatonin receptor agonist. With the addition of guanosine-5′- O-(3-thiophosphate) in the pipette solution, melatonin caused a stronger activation effect on the K + channels, and an irreversible increase of the current amplitude in some granule cells tested. Pretreatment of cells with PTX suppressed the action of melatonin on the K + current in most granule cells studied. In addition, the activation curves and inactivation curves tested with the steady-state activation and inactivation protocols were unchanged by melatonin, suggesting that melatonin did not modulate the channel’s activation and inactivation properties. Our results demonstrated the presence of a functional melatonin receptor in cultured cerebellar granule cells from neonatal cerebellum. Activating the receptor can modulate the outward K + currents by coupling to a PTX-sensitive G protein.