The mechanism of action of adenosine at the level of atrial myocardium has been a matter of debate. Electrophysiological studies showed that adenosine increases K+ efflux which may reduce Ca2+ influx, indirectly, by shortening the myocardial action potential. Recently some authors proposed that adenosine also depresses Ca2+ influx by a direct action on the L calcium channel, but, this effect being lower than that on voltage-dependent K+ channels, it was considered of minor importance. The effect of adenosine and its stable analogues was studied in the presence of the dihydropyridine Bay K 8644, a highly specific L-type calcium channel agonist, on isolated guinea-pig atria. The inotropic effect of the calcium channel activator was found to be antagonized by adenosine A1-receptor agonists. Binding studies showed that the effect on Bay K 8644 was not due to the interaction between adenosine analogues and dihydropyridines at the level of a common receptor site on L-type Ca2+ channels. Inhibitors of K+ channels did not antagonize the effect of adenosine analogues against Bay K 8644. Experimental conditions aimed to unmask an effect on slow Ca2+ currents (i.e. K+ depolarized paced atria), further supported that adenosine analogues may act in atria as negative modulators on L-type Ca2+ channels. Finally, the use of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a highly specific A1-receptor antagonist, demonstrated that the antagonism of Bay K 8644 by adenosine analogues is strictly dependent on A1 receptors. The above data support the possibility of a dual signal transduction pathway to ion channels (K+ and Ca2+) linked to A1 receptors in atrial myocardium

Adenosine: a natural modulator of L-type calcium channels in atrial myocardium?

RAGAZZI, EUGENIO;CAPARROTTA, LAURA
1991

Abstract

The mechanism of action of adenosine at the level of atrial myocardium has been a matter of debate. Electrophysiological studies showed that adenosine increases K+ efflux which may reduce Ca2+ influx, indirectly, by shortening the myocardial action potential. Recently some authors proposed that adenosine also depresses Ca2+ influx by a direct action on the L calcium channel, but, this effect being lower than that on voltage-dependent K+ channels, it was considered of minor importance. The effect of adenosine and its stable analogues was studied in the presence of the dihydropyridine Bay K 8644, a highly specific L-type calcium channel agonist, on isolated guinea-pig atria. The inotropic effect of the calcium channel activator was found to be antagonized by adenosine A1-receptor agonists. Binding studies showed that the effect on Bay K 8644 was not due to the interaction between adenosine analogues and dihydropyridines at the level of a common receptor site on L-type Ca2+ channels. Inhibitors of K+ channels did not antagonize the effect of adenosine analogues against Bay K 8644. Experimental conditions aimed to unmask an effect on slow Ca2+ currents (i.e. K+ depolarized paced atria), further supported that adenosine analogues may act in atria as negative modulators on L-type Ca2+ channels. Finally, the use of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a highly specific A1-receptor antagonist, demonstrated that the antagonism of Bay K 8644 by adenosine analogues is strictly dependent on A1 receptors. The above data support the possibility of a dual signal transduction pathway to ion channels (K+ and Ca2+) linked to A1 receptors in atrial myocardium
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11577/2481960
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