Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova / Rossiiskaia akademiia nauk 2011-11-01

[Mechanism of the slow inotropic response of the mouse atrium mediated by the beta2-adrenoreceptor].

Iu G Odnoshivkina, A M Petrov, A L Zefirov

Index: Ross. Fiziol. Zh. Im. I. M. Sechenova 97(11) , 1223-36, (2011)

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Abstract

The abundant beta2-adrenoceptors (AR) expression was revealed in the mouse atrial cardiomyocytes, albeit its function is poorly understood. Recently we revealed the slow developing (for 20-40 min) positive inotropic effect in the mouse atrium which was induced by the specific agonist of the beta2-adrenoceptors (5 mkM fenoterol) and the task of this study involved investigation of the found effect. It was shown that stimulation of beta2-AR is enough for rapid triggering of up-regulation of two signalling pathways that have the opposite influence on the contraction force. On one hand, activation of the adenylate cyclase--protein kinase A cascade occurs leading to increasing of intracellular Ca2+ concentration and amplitude of contraction; on the other hand, activation of the NO-synthase and enhance of NO production occurs which prevents the potentiating of the contraction force. During the first 15-20 minutes, superposition of these activation effects was revealed, which prevented the contraction strength increasing. Then the positive inotropic effects occurred due to the decreasing of NO production. It was shown that L-type Ca-channels and ryanodine receptors were the key targets incorporated in the beta2 adrenoreceptors signalling puzzle.