Modulation of noninactivating K+ channels in rat cerebellar granule neurons by halothane, isoflurane, and sevoflurane.

Abstract:

UNLABELLED: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 approximately 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 micro M) 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 micro M), which increased outward currents by 22%, 47%, 52%, and 60%, respectively (n = 5; P < 0.05; ANOVA). Sevoflurane 518 micro M 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. IMPLICATIONS:The volatile anesthetics halothane, isoflurane, and sevoflurane, reversibly enhanced a noninactivating outwardly rectifying K(+) current in rat cerebellar granule neurons. These findings support a model of anesthesia that includes a site of action at baseline K(+) channels.

journal_name

Anesth Analg

journal_title

Anesthesia and analgesia

authors

Shin WJ,Winegar BD

doi

10.1213/01.ane.0000055365.31940.0a

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

1340-4, table of contents

issue

5

eissn

0003-2999

issn

1526-7598

journal_volume

96

pub_type

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