HE EFFECT OF PROBENECID ON α-1-ADRENOCEPTOR STIMULATION INDUCED PROARRHYTHMIC CONDUCTION IN THE ATRIOVENTRICULAR NODE OF RAT HEART

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Cardiac tissue contains adrenergic receptors (AR) not only of the beta type, but also of the alpha type (α-AR). Both types of ARs play signifi cant role in regulation of cardiomyocytes electrophysiology in diff erent parts of the heart, including the atrioventricular node (AVN). An augmentation of α1-AR mediated component of adrenergic signaling results in impaired conduction of excitation in the heart and onset of various rhythm disturbances including AVNassociated arrhythmias. The activation of α1-AR facilitates anionic transmembrane transport causing electrophysiological changes in myocytes. Current study is aimed to the investigation of the eff ects of anion/chloride blockade on α1-AR-mediated proarrhythmic alteration of AVN functioning. Functional characteristics of AVN including AVN conduction time, AVN refractoriness and the AVN conduction alterations were examined via recording of surface electrograms in Langendorff -perfused isolated rat heart (Wistar, 250 ± 30 g). Phenylephrine was used as α1-AR agonist. Probenecid demonstrating anion/chloride transmembrane conductance blocking activity was used to modify Phe-induced α1-AR-mediated eff ects in AVN. The activation of α1-AR by Phe results in a signifi cant increase in the duration of AV intervals (N = 10, p < 0.001) and eff ective refractory period (ERP) in the AVN (by 9.8% ± 1.2%, n = 10, p < 0.001). Also, Phe induces AV-blocks of conduction and oscillations in atrioventricular delay (N = 10) at the stimulation rates close to ERP. Probenecid signifi cantly reduces the magnitude of AVD oscillations during non-stationary conduction in the AV node. In addition, probenecid attenuates ERP prolongation caused by Phe (107 ± 4 ms, N = 6) and 114.2 ± 5.35 ms (N = 10) in presence of only Phe and Phe with probenecid, respectively, returning its values toward typical for normal conditions. In conclusion, probenecid maintains physiological mode of AVN conduction when α1-AR are stimulated. This also suggests that chloride ion channels and anion carriers may contribute to the α1-AR-mediated AVN arrhythmias.