Modulation by 4-aminopyridine and calcium on the effect of adenosine on isolated spontaneously beating rat atria.
OBJECTIVE
The functional role of Ca2+ in pacemaker depolarization and in contraction was studied by challenging the inhibitory actions of adenosine to 4-AP and Ca2+ in the spontaneously beating rat atria.


METHODS
Studies were performed in adenosine-treated (0.3-100 microg/ml), adenosine + 4-aminopyridine (4-AP) (4mM)-treated, and Ca2+ (3.6mM or 400 microg/ml)-treated groups. All values were expressed as mean +/- S.E.M. Statistical analysis was done using Students t-test, where p < 0.05 was considered significant.


RESULTS
Adenosine (0.3-100 microg/ml) dose-dependently depressed both the beating frequency and contractility, more powerfully on the latter. 4-AP (4 mM) and Ca2+ (3.6 mM or 400 microg/ml) respectively increased force of contraction (203.4% and 199.3%) and spontaneous beating frequency (104.9% and 111.3%). 4-AP and Ca2+ significantly antagonized the inhibitory actions of adenosine on cardiac processes, more strongly on contractility and with 4-AP more potent than Ca2+.


CONCLUSIONS
(1) cardiac contractility was more responsive than pacemaker activity to the inhibitory action of adenosine, (2) 4-AP and Ca2+ acted to antagonize cardiac inhibition induced by adenosine, (3) the potency of antagonism appeared to be higher with 4-AP, and (4) the antagonism of adenosine by 4-AP on beating frequency is stronger with respect to contractility and is variable with Ca2+.
Küçükhüseyin
C
C
Department of Pharmacology and Clinical Pharmacology, Cerrahpaşa Faculty of Medicine, University of Istanbul 34750 Istanbul, Turkey. tahic@istanbul.edu.tr
Bozan
G
G
D015761:4-Aminopyridine / Q000378:metabolism / Q000494:pharmacology*; D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D015761:4-Aminopyridine; D000241:Adenosine; D002118:Calcium