Ionic mechanisms of the effect of adenosine on single rabbit atrioventricular node myocytes

Rankin, A.C., Martynyuk,, A.E., Workman, A.J. and Kane, K.A. (1997) Ionic mechanisms of the effect of adenosine on single rabbit atrioventricular node myocytes. Canadian Journal of Cardiology, 13(12), pp. 1183-1187.

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The ionic mechanisms underlying the negative dromotropic effect of adenosine were studied in calcium-tolerant myocytes isolated from the region of the rabbit atrioventricular (AV) node. Action potentials and membrane currents were recorded by using the whole cell patch clamp technique. Adenosine (1 to 50 m M) abolished the spontaneous activity of AV node myocytes with hyperpolarization of the membrane potential. Voltage clamp experiments showed that adenosine induced an inwardly rectifying, time-independent potassium current. These effects were antagonized by 8-cyclopentyl-1,3-dipropylxanthine and produced by ribose 5-phosphate isomerase A, indicating that they were mediated by the A1 adenosine receptor. Adenosine also had a small direct inhibitory action on the inward calcium current (I<sub>Ca</sub>) but had a more marked indirect action following stimulation of the calcium current by isoprenaline. The isoprenaline-induced increase in I<sub>Ca</sub> was abolished in the presence of adenosine 10 m M. In cells pretreated with the nitric oxide synthase inhibitor N<sup>w</sup> -nitro-L-arginine methyl ester (L-NAME), the isoprenaline-induced increase in I<sub>Ca</sub> was not reduced by the addition of adenosine. Coincubation of the cells with L-NAME plus L-arginine (the endogenous substrate of nitric oxide synthase) restored the adenosine-induced attenuation of I<sub>Ca</sub>. A membrane permeable analogue of cGMP, 8Br cGMP, an inhibitor of cGMP-stimulated phosphodiesterase, prevented the antiadrenergic effect of adenosine. These results suggest that adenosine activates guanylyl cyclase following the production of nitric oxide, and the subsequent stimulation of phosphodiesterase enhances the breakdown of isoprenaline-elevated cAMP leading to a reduction in the stimulated I<sub>Ca</sub>. In conclusion, the important ionic mechanisms of the actions of adenosine on AV nodal cells are a direct effect, with activation of a potassium conductance and an indirect antiadrenergic effect on I<sub>Ca</sub>, which is mediated by nitric oxide production and phosphodiesterase stimulation.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Workman, Dr Antony
Authors: Rankin, A.C., Martynyuk,, A.E., Workman, A.J., and Kane, K.A.
Subjects:Q Science > QL Zoology
Q Science > QD Chemistry
College/School:College of Medical Veterinary and Life Sciences
Journal Name:Canadian Journal of Cardiology
Publisher:Pulsus Group Inc

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