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Effect of alpha‐dihydro‐grayanotoxin‐II on the electrical activity of the rabbit sino‐atrial node.
Author(s) -
Nakao M,
Seyama I
Publication year - 1984
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1984.sp015490
Subject(s) - chemistry , tetrodotoxin , conductance , voltage clamp , biophysics , reversal potential , membrane potential , analytical chemistry (journal) , patch clamp , physics , biology , biochemistry , receptor , chromatography , condensed matter physics
The effect of alpha‐dihydro‐grayanotoxin‐II (GTX) on the electrical activity of rabbit sino‐atrial (s.a.) node cells was studied by the two‐micro‐electrode voltage‐clamp technique. GTX, at concentrations between 3 and 10 microM, suppressed the spontaneous beating of the s.a. node. On subsequent application of 1 microM‐tetrodotoxin (TTX), the membrane repolarized and spontaneous beating was restored, whereas the maximum rate of rise and the frequency of the action potential were reduced slightly. The additional application of adrenaline (0.55 microM) (in the presence of GTX plus TTX) completely restored the normal electrical activity of the s.a. node cells. Voltage‐clamp experiments revealed that GTX, in this concentration range, reduced the maximum conductance of slow inward current by 15%, and did not affect the outward current system. The steady‐state inactivation curve for the slow inward current was not shifted along the membrane potential axis, whereas that for the fast inward Na current was shifted in the direction of hyperpolarization. In addition, GTX generated a time‐independent current (IGTX) which could be eliminated by the application of TTX. The current‐voltage relation for IGTX was linear and crossed the voltage axis at +4.0 +/‐ 2.2 mV (n = 4). The application of GTX in a concentration range above 30 microM abolished all gated inward and outward currents of the s.a. node. The results suggest that the GTX‐induced sinus arrest is mainly due to an increase in the membrane permeability to Na ions and that this increase in permeability is due to conversion of the normal fast Na channel into a modified one, which lacks an inactivation process.