Human cardiac sodium channels are affected by pentobarbital

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 (f_max = −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.