| Modulation of Baseline Potassium Channels in Cerebellar Granule Neurons of Sprague-Dawley Rats by Sevoflurane. |
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Woo Jong Shin, Bruce D Winegar |
1Department of Anesthesiology, College of Medicine, Hanyang University, Seoul, Korea
2Department of Anesthesia and Perioperative Care, School of Medicine, University of California San Fancisco, San Francisco, USA. |
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| Abstract |
BACKGROUND
Volatile general anesthetics have been widely used to produce reversible unconsciousness and analgesia in clinical practice over the last one hundred years, but the basic mechanism of anesthetic action is not yet completely understood. In addition to the well known mechanism of GABAA and glycine channels, accumulating evidence indicates that neuronal baseline K+ channels are also activated by volatile anesthetics. The goal of this study was to test the hypothesis that sevoflurane, one of the newly developed volatile anesthetics, activates baseline potassium channnels in the cerebellar granule neurons of rats.
METHODS
Whole cell measurement techniques were performed from cultured cerebellar granule neurons of seven day old male Sprague-Dawley rats using patch clamp techniques to see the effects of two MACs of sevoflurane on baseline K+ channels. Holding potentials were set to 20 mV and collect pulses from 90 to 90 in 10 mV increments of 300 ms duration.
The electrode filling solution contained (in mM) 150 KOH, 105 aspartic acid, 3 NaCl, 10 HEPES, 86 glucose, 1 EGTA, 5 MgCl2 (pH 7.4) and standard saline were used as bath solution. The bath contained 150 NaCl, 3 KCl, 10 HEPES, 14 glucose, 1 EGTA, 5 MgCl2 (pH 7.4).
RESULTS
Analysis of multiple patch clamp experiments showed the presence of outward-rectifying K+ selective ion channels with a conductance of 1.064 +/- 0.32 nS (n = 10) at depolarized potentials. Cerebellar granule neurons exhibit rapid rising, noninactivating, outward-rectifying currents.
These channels are insensitive to conventional K+ channel blockers. Clinically relevant concentrations of sevoflurane (518nM) increased the baseline K+ channel outward currents from the control value by 225% in a standard saline perfusate (n = 10, P < 0.05, paired t-test). Channel activity enhanced during the duration of the exposure period to sevoflurane returned to the baseline activity level quickly upon wash.
CONCLUSIONS
These outward-rectifying whole cell I V curves are consistent with the properties of tandem pore K+ channels. Activation of baseline K+ channels in central neurons by two MACs of sevoflurane causes membrane hyperpolarization and increases neuronal input conductances providing an additional inhibitory mechanism that could contribute to the overall central depressant effects of this compound. |
| Key Words:
Cerebellar granule neurons; patch clamp; potassium channel; sevoflurane |
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