The Role of Adenosine Receptors and L-Type Calcium Channels in the Regulation of the Mediator Secretion in Mouse Motor Synapses

Tarasova, E.O.; Miteva, A.S.; Gaydukov, A.E.; Balezina, O.P.

Авторы: Tarasova E.O., Miteva A.S., Gaydukov A.E., Balezina O.P.
Журнал: Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology
Том: 9
Номер: 4
Год издания: 2015
Издательство: Pleiades Publishing, Ltd
Местоположение издательства: Road Town, United Kingdom
Первая страница: 318
Последняя страница: 328
DOI: 10.1134/S1990747815050141
Аннотация: The changes in spontaneous and evoked neurotransmitter release caused by agonists and antagonists of A1- and A2A-subtypes of adenosine receptors combined with inhibition of some enzymes and voltage-dependent calcium channels of L-type were studied in mouse diaphragm motor synapses using intracellular microelectrode recordings of miniature endplate potentials (MEPPs) and evoked endplate potentials (EPPs). Simultaneous activation of presynaptic A1- and A2A-receptors during short-term rhythmic activity of motor synapses was shown for the first time. Activation of A1-receptor’s prevails, and it is followed by downregulation of ACh release due to inhibition of intracellular cascade which involves proteinkinase A (PKA) and L-type voltage-dependent calcium channels. Activation of A2A-receptors with their agonist CGS-21680 caused upregulation of ACh secretion due to enhancement of PKA activity followed by activation of L-type voltage-dependent calcium channels. The mechanism of evoked release potentiation when A1-receptors are blocked or A2A-receptor’s activity prevails over A1-receptors involves calcium release from ryanodine sensitive intracellular calcium stores coupled with PKA and L-type voltage-dependent calcium channels activation. It was found out that proteinphosphatase calcineurin participates in downregulation of L-type voltage-dependent calcium channels irrespective of the A1-receptors. It was shown for the first time that disinhibition of L-type voltage-dependent calcium channels caused by calcineurin inhibition requires participation of A2A-receptor’s activity and PKA activity. In conclusion, reciprocal interactions between presynaptic A1- and A2A-receptors and their action on ACh release were shown in motor synapses. These interactions are mediated by the following cascade: PKA → L-type voltage-dependent calcium channels → ryanodine receptors of calcium stores. Final effect on neurotransmitter release depends on conditions of coactivation of these receptors and interplay of enzymes and L-type voltage-dependent calcium channels within synaptic terminals.
Добавил в систему: Гайдуков Александр Евгеньевич

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The Role of Adenosine Receptors and L-Type Calcium Channels in the Regulation of the Mediator Secretion in Mouse Motor Synapsesстатья

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