Block of sodium current by heptanol in voltage-clamped canine cardiac Purkinje cells

Abstract

Heptanol blocks sodium current (I(Na)) in nerve, but its effects on cardiac I(Na) have not been well characterized. Block of I(Na) by heptanol was studied in 16 internally perfused voltage-clamped cardiac Purkinje cells at reduced Na+ (45 mM outside, 0 mM inside). Heptanol block of peak sodium conductance was well described by a single-site binding curve with half block at 1.3 mM (20°C) and showed no 'use dependence.' With 1.5 mM heptanol, block increased slightly by 0.7%/°C from 10°C to 27°C. With 3.0 mM heptanol, steady-state availability shifted by 9.4 ± 1.3 mV (n = 6) in the hyperpolarizing direction, and steady-state activation shifted by 8.3 ± 2.2 mV (n = 5) in the depolarizing direction, thus closing off the I(Na) 'window current.' Heptanol also decreased the time to peak and accelerated the decay of I(Na). Similar results were found with octanol at lower concentrations. These alcohols have important effects on cardiac I(Na) at concentrations used in studies for cellular uncoupling in heart.