Effect of 2-nicotinamidethyl nitrate (SG-75) on the membrane potential of left atrial muscle fibres of the dog

Summary

• 1. 2-Nicotinamidethyl nitrate (SG-75) (10⁻⁶–10⁻⁴ mol/l) and methacholine (MeCh) (10⁻⁷–10⁻⁵ mol/l) hyperpolarized the resting membrane potential, and produced increases in amplitude and maximum rate of rise and a decrease in duration of the action potential of left atrial muscle fibres of the dog.

• 2. Changes in membrane potentials produced by SG-75 were not modified by atropine at a concentration (3×10⁻⁷ mol/l) which greatly antagonized those induced by MeCh.

• 3. The decrease in resting membrane potential for a 10-fold increase in extracellular K⁺ concentration ([K⁺]₀) was greater in the presence than in the absence of SG-75 or MeCh.

• 4. SG-75- and MeCh-induced changes in membrane potentials were not affected by the replacement of NaCl by Na isethionate in perfusion fluid.

• 5. SG-75- and MeCh-induced changes in membrane potentials were not modified by ouabain (10⁻⁶ mol/l).

• 6. The “slow response” of left atrial muscle fibres was obtained by increasing the [K⁺]₀ to 27 mM in the presence of isoprenaline (10⁻⁶ mol/l). SG-75 and MeCh primarily produced a decrease in duration of the “slow response”. At higher concentrations SG-75 and MeCh hyperpolarized the resting membrane potential and decreased the amplitude and maximum rate of rise of the “slow response”. Unlike SG-75 and MeCh, verapamil primarily decreased the amplitude and maximum rate of rise of the “slow response” without changes in duration of the “slow response” and resting membrane potential.

• 7. The above results suggest that the mechanism of action of SG-75 on left atrial muscle fibres may be an increase in potassium conductance of the membrane without mediation through muscarinic receptors.