Modulation of Noninactivating K+ Channels in Rat Cerebellar Granule Neurons by Halothane, Isoflurane, and Sevoflurane

• Published in: Anesthesia and analgesia Vol. 96; no. 5; pp. 1340 - 1344
• Main Authors: Shin, Woo-Jong, Winegar, Bruce D.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD International Anesthesia Research Society 01.05.2003; Lippincott
• Subjects: Anesthetics, Inhalation - pharmacology; Anesthetics. Neuromuscular blocking agents; Animals; Biological and medical sciences; Cerebellum - cytology; Cerebellum - drug effects; Cerebellum - metabolism; Halothane - pharmacology; In Vitro Techniques; Isoflurane - pharmacology; Male; Medical sciences; Membrane Potentials - drug effects; Methyl Ethers - pharmacology; Neurons - drug effects; Neurons - metabolism; Neuropharmacology; Patch-Clamp Techniques; Pharmacology. Drug treatments; Potassium Channel Blockers - pharmacology; Potassium Channels - drug effects; Rats; Rats, Sprague-Dawley; Sevoflurane; Cerebellum; Volatile compound; Cell culture; Granule neuron; Rat; Potassium ion; Rodentia; Central nervous system; Halothane; Electrophysiology; Nervous system; Ionic channel; In vitro; Isoflurane; Sevoflurane; Vertebrata; Mammalia; General anesthetic; Animal; Mechanism of action; Halogen Organic compounds
• ISSN: 0003-2999; 1526-7598
• DOI: 10.1213/01.ANE.0000055365.31940.0A

Neuronal baseline K+ channels were activated by several volatile anesthetics. Whole-cell recordings from cultured cerebellar granule neurons of 7-day-old male Sprague-Dawley rats showed outward-rectifying K+ currents with a conductance of ∼1.1 ± 0.3 nS (n = 20) at positive potentials. The channel activity was noninactivating, exhibited no voltage gating, and was insensitive to conventional K+ channel blockers. Clinically relevant concentrations of halothane (112, 224, 336, and 448 μM) dissolved in Ringer’s solution increased outward currents by 29%, 50%, 63%, and 94%, respectively (n = 5;P < 0.05; analysis of variance [ANOVA]). Similar increases in currents were produced by isoflurane (274, 411, 548, and 822 μM), which increased outward currents by 22%, 47%, 52%, and 60%, respectively (n = 5;P < 0.05; ANOVA). Sevoflurane 518 μM increased outward currents by 225% (n = 10;P < 0.05; ANOVA). In all experiments, channel activity quickly returned to baseline levels during wash. The outward-rectifying whole-cell current-voltage curves were consistent with the properties of anesthetic-sensitive KCNK channels. These results support the idea that noninactivating baseline K+ channels are important target sites of volatile general anesthetics.