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Human cardiac sodium channels are affected by pentobarbital

Published online by Cambridge University Press:  16 August 2006

H. C. Wartenberg
Affiliation:
Klinik und Poliklinik für Anästhesiologie und spezielle Intensivmedizin, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany Correspondence: H. C. Wartenberg.
J. P. Wartenberg
Affiliation:
Klinik und Poliklinik für Anästhesiologie und spezielle Intensivmedizin, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany
B. W. Urban
Affiliation:
Klinik und Poliklinik für Anästhesiologie und spezielle Intensivmedizin, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany
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Abstract

Background and Objective To investigate the response to general anaesthetics of different sodium channel subtypes, we examined the effects of pentobarbital, a close thiopental analogue, on single sodium channels from human ventricular muscle and compared them with existing data from human brain channels.

Methods Sodium channels from preparations of human ventricular muscle were incorporated into planar lipid bilayers in the presence of batrachotoxin, a sodium channel activator. Single channel currents were recorded in symmetrical 100mmolL−1 and 500mmolL−1 NaCl before and after the addition of the anaesthetic pentobarbital (0.34–1.34mmolL−1).

Results The blocking effect of pentobarbital on the fractional open time had an IC50 of 690 μmol L−1 in 500 mmolL−1 NaCl, whereas it had a significantly lower IC50 of 400 μmol L−1 in 100 mmolL−1 NaCl. Pentobarbital caused a significant shift of steady-state activation to hyperpolarized potentials (fmax = −42 mV, IC50=2 mmolL−1). This effect was independent of NaCl concentration.

Conclusion Despite pharmacological and electrophysiological differences between human cardiac and human brain sodium channels their responses to pentobarbital are similar. The finding of channel block being dependent on the electrolyte concentration is novel for sodium channels.

Type
Original Article
Copyright
2001 European Society of Anaesthesiology

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