Mechanisms of hydrogen sulfide (H2S) action on synaptic transmission at the mouse neuromuscular junction. (10th September 2015)

• Record Type: Journal Article
• Authors: Gerasimova, E.; Lebedeva, J.; Yakovlev, A.; Zefirov, A.; Giniatullin, R.; Sitdikova, G.
• Is Part Of: Neuroscience. Volume 303(2015)
• Page Start: 577
• Page End: 585
• Publication Date: 2015-09-10
• Subjects: AOAA aminooxyacetic acid -- BAPTA-AM 1, 2-bis(2-aminophenoxy)ethane-N, N, N′, N′-tetraacetic acid tetrakis acetoxymethyl ester -- CBS cystathionine β-synthase -- CO carbon monoxide -- CSE cystathionine γ-lyase -- EGTA-AM ethylene glycol-bis(2-aminoethylether)-N, N, N′, N′-tetraacetic acid acetoxymethyl ester -- EPCs end-plate currents -- EPPs end-plate potentials -- H2S hydrogen sulfide -- HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid -- MDL 12330A MDL 12, 330A hydrochloride -- MEPCs miniature end-plate currents -- MEPPs miniature end-plate potentials -- NaHS sodium hydrosulfide -- NO nitric oxide -- pCPT-cAMP 8-(4-chlorophenylthio)-adenosine 3′, 5′-cyclic monophosphate -- RyR ryanodine receptors -- β-CA β-cyano-l-alanine; hydrogen sulfide -- neuromuscular junction -- transmitter release -- l-cysteine -- adenylate cyclase -- ryanodine receptors; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2015.07.036
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: H2 S increases spontaneous and evoked transmitter release from mammalian motor nerve endings. The precursor of H2 S shares the facilitatory effect whereas inhibitors of H2 S synthesis exerted the opposite action. Action of H2 S is mediated by cAMP cascade with involvement of ryanodine receptors. Abstract: Hydrogen sulfide (H2 S) is a widespread gasotransmitter also known as a powerful neuroprotective agent in the central nervous system. However, the action of H2 S in peripheral synapses is much less studied. In the current project we studied the modulatory effects of the H2 S donor sodium hydrosulfide (NaHS) on synaptic transmission in the mouse neuromuscular junction using microelectrode technique. Using focal recordings of presynaptic response and evoked transmitter release we have shown that NaHS (300 μM) increased evoked end-plate currents (EPCs) without changes of presynaptic waveforms which indicated the absence of NaHS effects on sodium and potassium currents of motor nerve endings. Using intracellular recordings it was shown that NaHS increased the frequency of miniature end-plate potentials (MEPPs) without changing their amplitudes indicating a pure presynaptic effect. Furthermore, NaHS increased the amplitude of end-plate potentials (EPPs) without influencing the resting membrane potential of muscle fibers.l -cysteine, a substrate of H2 S synthesis induced, similar to NaHS, an increase of EPC amplitudes whereas inhibitors of H2 S synthesis (β-cyano-l -alanine and aminooxyacetic acid) had the opposite effect. Inhibition of adenylate cyclase using MDL 12, 330A hydrochloride (MDL 12, 330A) or elevation of cAMP level with 8-(4-chlorophenylthio)-adenosine 3′, 5′-cyclic monophosphate (pCPT-cAMP) completely prevented the facilitatory action of NaHS indicating involvement of the cAMP signaling cascade. The facilitatory effect of NaHS was significantly diminished when intracellular calcium (Ca 2+ ) was buffered by 1, 2-bis(2-aminophenoxy)ethane-N, N, N′, N′-tetraacetic acid tetrakis acetoxymethyl ester (BAPTA-AM) and ethylene glycol-bis(2-aminoethylether)-N, N, N′, N′-tetraacetic acid acetoxymethyl ester (EGTA-AM). Activation of ryanodine receptors by caffeine or ryanodine increased acetylcholine release and prevented further action of NaHS on transmitter release, likely due to an occlusion effect. Inhibition of ryanodine receptors by ryanodine or dantrolene also reduced the action of NaHS on EPC amplitudes. Our results indicate that in mammalian neuromuscular synapses endogenously produced H2 S increases spontaneously and evoked quantal transmitter release from motor nerve endings without changing the response of nerve endings. The presynaptic effect of H2 S appears mediated by intracellular Ca 2+ and cAMP signaling and involves presynaptic ryanodine receptors.