The mechanism of the inotropic action of striatoxin, a novel polypeptide toxin from a marine snail, in isolated cardiac muscle.
1. Striatoxin (StTX), a novel polypeptide from a marine snail, caused a dose-dependent increase in contractility in the isolated atria of guinea-pig and rat in the concentration-range of 2 x 10(-9) to 3 x 10(-8)M and 3 x 10(-6)M, respectively. 2. In guinea-pig atria, the StTX-induced inotropic effect was inhibited by tetrodotoxin but not by cimetidine or chlorpheniramine. Practolol, propranolol or reserpine caused only partial block of this inotropic action. 3. In isolated single cells from rat hearts, StTX caused an increase in the degree and the rate of contraction. 4. In guinea-pig atria, StTX provoked action potentials with a plateau phase of long duration without affecting the maximum rate of rise, the amplitude of action potential and the resting membrane potential. This prolongation was also reversed by tetrodotoxin. 5. In guinea-pig cardiac myocytes, whole-cell patch-clamp experiments showed that StTX slowed Na channel inactivation without affecting the time course of channel activation. The voltage dependence of Na currents was not altered by StTX. 6. The residual currents, but not peak currents were markedly enhanced by StTX. 7. These results suggest that StTX causes prolongation of the action potential duration probably due to slowed inactivation of Na inward currents and enhanced residual currents and that this may result in an increase in Ca2+ availability in cardiac muscle cells. This could explain the cardiotonic action of StTX.
Ohizumi
Y
Y
Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
Kobayashi
M
M
Muroyama
A
A
Nakamura
H
H
Kobayashi
J
J
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis; D006023:Glycoproteins / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D008978:Mollusk Venoms / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000032:analysis; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D002316:Cardiotonic Agents; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D008978:Mollusk Venoms; D002744:Chlorpheniramine; D013779:Tetrodotoxin; D002927:Cimetidine; C034992:striatoxin protein, Conus striatus; D012110:Reserpine; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000254:Sodium-Potassium-Exchanging ATPase