In atrial myocytes of the guinea pig, the effects of adenosine (Ado) and acetylcholine (ACh) on Ca currents (ICa) were investigated with the patch-electrode whole cell clamp technique. ICa was dissected from net currents by blocking K currents (IK) with intra- and extracellular Cs ions. ICa was considered as "basal" ICa, since it was not prestimulated by beta-agonists (isoproterenol). T-channel Ca currents were insensitive to Ado or ACh. The antagonism of L-channel Ca currents was maximal with 10 microM Ado or 3 microM ACh, which reduced basal ICa by 35%. From the concentration dependence, a dissociation constant (KD) value of 1.1 microM Ado and a Hill coefficient of -3 were obtained. Ado and ACh were not additive but saturative in reducing basal ICa. Reduction of basal ICa did not modify inactivation time-course, steady-state activation or inactivation, suggesting that Ado reduces the number of functional Ca channels. In myocytes with unblocked IK (KCl electrodes), 3 microM Ado (1 microM ACh) reduced ICa by 30% but increased IK by 300%. It is concluded that the K-agonistic rather than the Ca-antagonistic effect accounts for hyperpolarization as well as for most of the shortening of the action potential and the negative inotropy.

Ca-antagonistic effects of adenosine in guinea pig atrial cells / Cerbai E;Klöckner U;Isenberg G. - In: AMERICAN JOURNAL OF PHYSIOLOGY. - ISSN 0002-9513. - STAMPA. - 255:(1988), pp. H872-H878.

Ca-antagonistic effects of adenosine in guinea pig atrial cells.

CERBAI, ELISABETTA;
1988

Abstract

In atrial myocytes of the guinea pig, the effects of adenosine (Ado) and acetylcholine (ACh) on Ca currents (ICa) were investigated with the patch-electrode whole cell clamp technique. ICa was dissected from net currents by blocking K currents (IK) with intra- and extracellular Cs ions. ICa was considered as "basal" ICa, since it was not prestimulated by beta-agonists (isoproterenol). T-channel Ca currents were insensitive to Ado or ACh. The antagonism of L-channel Ca currents was maximal with 10 microM Ado or 3 microM ACh, which reduced basal ICa by 35%. From the concentration dependence, a dissociation constant (KD) value of 1.1 microM Ado and a Hill coefficient of -3 were obtained. Ado and ACh were not additive but saturative in reducing basal ICa. Reduction of basal ICa did not modify inactivation time-course, steady-state activation or inactivation, suggesting that Ado reduces the number of functional Ca channels. In myocytes with unblocked IK (KCl electrodes), 3 microM Ado (1 microM ACh) reduced ICa by 30% but increased IK by 300%. It is concluded that the K-agonistic rather than the Ca-antagonistic effect accounts for hyperpolarization as well as for most of the shortening of the action potential and the negative inotropy.
1988
255
H872
H878
Cerbai E;Klöckner U;Isenberg G
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/656747
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