Summary
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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.
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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.
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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.
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4.
SG-75- and MeCh-induced changes in membrane potentials were not affected by the replacement of NaCl by Na isethionate in perfusion fluid.
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5.
SG-75- and MeCh-induced changes in membrane potentials were not modified by ouabain (10−6 mol/l).
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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.
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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.
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Yanagisawa, T., Taira, N. Effect of 2-nicotinamidethyl nitrate (SG-75) on the membrane potential of left atrial muscle fibres of the dog. Naunyn-Schmiedeberg's Arch. Pharmacol. 312, 69–76 (1980). https://doi.org/10.1007/BF00502577
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DOI: https://doi.org/10.1007/BF00502577