T-channels and Na+,Ca2+-exchangers as components of the Ca2+-system of the myocardial activity regulation of the frog Rana temporaria].

I V Shemarova, S V Kuznetsov, I N Demina, V P Nesterov

Zhurnal evoliutsionnoĭ biokhimii i fiziologii 2009 May-Jun

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Earlier we have shown that regulation of rhythm and strength of the frog heart contractions, mediated by transmitters of the autonomic nervous system, is of the Ca2+-character. In the present work, we studied chrono- and inotropic effect of verapamil--an inhibitor of Ca2+-channels of the L-type, of nickel chloride--an inhibitor of Ca2+-channels of the T-type, and of Na+,Ca2+-exchangers as well as of adrenaline and acetylcholine (ACh) after nickel chloride. It has been found that the intracardially administered NiCl2 at a dose of 0.01 microg/kg produced a sharp fall of amplitude of action potential (AP) and an almost twofold deceleration of heart rate (HR). The intracardiac administration of NiCl2 (0.01 microg/kg) on the background of action of verapamil (6 mg/kg, i/m) led as soon as after 3 min to even more prominent HR deceleration and to further fall of the AP amplitude by more than 50% as compared with norm. The intracardiac administration of adrenaline (0.5 mg/kg) partly restored the cardiac activity. However, preservation of the myocardium electrical activity in such animals was brief and its duration did not exceed several minutes. Administration of Ni2+ on the background of acetylcholine (3.6 mg/kg) led to almost complete cessation of cardiac activity. As soon as after 3 min after injection of this agent the HR decreased to 2 contractions/min. On EG, the 10-fold fall of the AP amplitude was recorded. The elucidate role of extra- and intracellular Ca2+ in regulation of heart contractions, isometric contraction of myocardium preparations was studied in response to action of NiCl2 (10-200 microM), verapamil (70 microM), adrenaline (5 microM), and acetylcholine (0.2 microM) after NiCl2. It is found that Ni2+ caused a dose-dependent increase of the muscle contraction amplitude. Minimal change of the contraction amplitude (on average, by 14.9% as compared with control) was recorded at a Ni2+ concentration of 100 microM. An increase of Ni2+ in the sample to 200 microM increased the cardiac contraction strength, on average, by 41%. The negative inotropic action of verapamil was essentially reduced by 100 microM Ni2+. Adrenaline added to the sample after Ni2+ produced stimulating effect on the cardiac muscle, with and almost twofold rise of the contraction amplitude. ACh (0.2 microM) decreased the cardiac contraction amplitude, on average, by 56.3%, whereas Ni2+ (200 microM) administered after ACh not only restored, but also stimulated partly the myocardial work. Within several parts of percent there was an increase of such isometric contraction parameters as amplitude of the muscle-developed effort, maximal rate, maximal acceleration, time of semirise and semifall. The obtained experimental results indicate that the functional activity of the frog pacemaker and contractile cardiomyocytes is regulated by the Ca2+-dependent mechanisms. Structure of these mechanisms includes the potential-controlled L- and T-channels of the plasma membrane as well as Na+,Ca2+-exchangers characteristic exclusively of contractile cardiomyocytes. The existence of these differences seems to be due to the cardiomyocyte morphological peculiarities that appeared in evolution at the stage of the functional cell specialization.

Citation

I V Shemarova, S V Kuznetsov, I N Demina, V P Nesterov. T-channels and Na+,Ca2+-exchangers as components of the Ca2+-system of the myocardial activity regulation of the frog Rana temporaria]. Zhurnal evoliutsionnoĭ biokhimii i fiziologii. 2009 May-Jun;45(3):319-28