Effect of alpha-dihydro-grayanotoxin-II on the electrical activity of the rabbit sino-atrial node. 1984

M Nakao, and I Seyama

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.

UI MeSH Term Description Entries
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D004224 Diterpenes Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate. Diterpene,Diterpenes, Cembrane,Diterpenes, Labdane,Diterpenoid,Labdane Diterpene,Norditerpene,Norditerpenes,Norditerpenoid,Cembranes,Diterpenoids,Labdanes,Norditerpenoids,Cembrane Diterpenes,Diterpene, Labdane,Labdane Diterpenes
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004837 Epinephrine The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS. Adrenaline,4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol,Adrenaline Acid Tartrate,Adrenaline Bitartrate,Adrenaline Hydrochloride,Epifrin,Epinephrine Acetate,Epinephrine Bitartrate,Epinephrine Hydrochloride,Epinephrine Hydrogen Tartrate,Epitrate,Lyophrin,Medihaler-Epi,Acetate, Epinephrine
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012849 Sinoatrial Node The small mass of modified cardiac muscle fibers located at the junction of the superior vena cava (VENA CAVA, SUPERIOR) and right atrium. Contraction impulses probably start in this node, spread over the atrium (HEART ATRIUM) and are then transmitted by the atrioventricular bundle (BUNDLE OF HIS) to the ventricle (HEART VENTRICLE). Sinuatrial Node,Sinus Node,Sino-Atrial Node,Sinu-Atrial Node,Node, Sino-Atrial,Node, Sinoatrial,Node, Sinu-Atrial,Node, Sinuatrial,Node, Sinus,Nodes, Sino-Atrial,Nodes, Sinoatrial,Nodes, Sinu-Atrial,Nodes, Sinuatrial,Nodes, Sinus,Sino Atrial Node,Sino-Atrial Nodes,Sinoatrial Nodes,Sinu Atrial Node,Sinu-Atrial Nodes,Sinuatrial Nodes,Sinus Nodes
D013779 Tetrodotoxin An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction. Fugu Toxin,Tarichatoxin,Tetradotoxin,Toxin, Fugu
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor

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