PT  - JOURNAL ARTICLE
AU  - Robert F. Furchgott
AU  - William Sleator, Jr.
AU  - Taisija de Gubareff
TI  - EFFECTS OF ACETYLCHOLINE AND EPINEPHRINE ON THE CONTRACTILE STRENGTH AND ACTION POTENTIAL OF ELECTRICALLY DRIVEN GUINEA PIG ATRIA
DP  - 1960 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 405--416
VI  - 129
IP  - 4
4099  - http://jpet.aspetjournals.org/content/129/4/405.short
4100  - http://jpet.aspetjournals.org/content/129/4/405.full
SO  - J Pharmacol Exp Ther1960 Aug 01; 129
AB  - Simultaneous recordings were made of mechanical and electrical changes in isolated, electrically driven left atria of guinea pigs. Action potentials were obtained using both extracellular and intracellular electrodes, and it has been possible to account in a qualitative manner for the configuration of extracellular action potentials on the basis of configuration of intracellular action potentials. With intracellular recording it was found that depression of contractile strength by acetylcholine was associated with a marked decrease in duration of the intracellular action potential. With extracellular recording this depression was usually asssociated with a shift in polarity of the repolarization wave of the extracellular action potential from the same polarity as that of the spike to the opposite polarity. The effects of acetylcholine on both contractile strength and action potential were potentiated markedly by physostigmine, and were effectively antagonized by atropine. The increase in contractile strength by epinephrine was associated with an increase in duration of the intracellular action potential, and with minor changes in configuration and usually some increase in duration of the repolarization phase of the extracellular action potential. Epinephrine was able to counteract completely the effect of acetylcholine in limited concentrations on contractile strength while only partially or weakly counteracting its effect on the action potential (either intracellular or extracellular). However, the effects of high concentrations of acetylcholine on contractile strength and action potentials could not be altered by epinephrine even at very high concentrations. On prolonged exposure to high concentrations of acetylcholine, whether in the presence or absence of epinephrine, a desensitization developed to the actions of acetylcholine on both contractile strength and action potential. The time course for recovery of full sensitivity after washout of the desensitizing dose was very prolonged. The finding that combinations of acetylcholine and epinephrine in appropriate concentrations can lead to a marked shortening of the action potential with no significant change in contractile strength has been discussed in relation to the hypothesis that the negative inotropic effect of acetylcholine is causally related to the shortening of the action potential produced by this agent. Also, the desensitization phenomenon with high concentrations of acetylcholine has been discussed, and the hypothesis presented that the desensitization results from a deactivation of cholinergic receptors during prolonged exposure to high concentrations of this agent.