Abstract
H2S is well-known as hypotensive agent, whether it is synthetized endogenously or administered systemically. Moreover, the H2S donor NaHS has been shown to inhibit vasopressor responses triggered by stimulation of preganglionic sympathetic fibers. In contradiction with this latter result, NaHS has been reported to facilitate transmission within sympathetic ganglia. To resolve this inconsistency, H2S and NaHS were applied to primary cultures of dissociated sympathetic ganglia to reveal how this gasotransmitter might act at different subcellular compartments of such neurons. At the somatodendritic region of ganglionic neurons, NaHS raised the frequency, but not the amplitudes, of cholinergic miniature postsynaptic currents via a presynaptic site of action. In addition, the H2S donor as well as H2S itself caused membrane hyperpolarization and decreased action potential firing in response to current injection. Submillimolar NaHS concentrations did not affect currents through Kυ7 channels, but did evoke currents through KATP channels. Similarly to NaHS, the KATP channel activator diazoxide led to hyperpolarization and decreased membrane excitability; the effects of both, NaHS and diazoxide, were prevented by the KATP channel blocker tolbutamide. At postganglionic sympathetic nerve terminals, H2S and NaHS enhanced noradrenaline release due to a direct action at the level of vesicle exocytosis. Taken together, H2S may facilitate transmitter release within sympathetic ganglia and at sympatho-effector junctions, but causes hyperpolarization and reduced membrane excitability in ganglionic neurons. As this latter action was due to KATP channel gating, this channel family is hereby established as another previously unrecognized determinant in the function of sympathetic ganglia.
Highlights
Cardiovascular disease is a leading cause of death worldwide with elevated blood pressure, raised blood lipids and glucose, as well as thrombosis and inflammation as major underlying pathophysiological risk factors (Tzoulaki et al, 2016)
To assess whether hydrogen sulfide (H2S) affects the membrane potential and/or action potential firing in superior cervical ganglia (SCG) neurons, cells were recorded in the perforated current-clamp mode to maintain intracellular signaling cascades potentially involved in the actions of the gas
H2S is steadily liberated from this donor, and the H2S concentrations achieved in physiological salt solutions amount to approximately 25% of that of NaHS itself (Sitdikova et al, 2014)
Summary
Cardiovascular disease is a leading cause of death worldwide with elevated blood pressure, raised blood lipids and glucose, as well as thrombosis and inflammation as major underlying pathophysiological risk factors (Tzoulaki et al, 2016). All three gasotransmitters attenuate tissue damage, for instance in the myocardial ischemia reperfusion injury model, and provide protective effects in the cardiovascular system, in particular vasodilation (Li et al, 2009). NO donors have been used in cardiovascular pharmacotherapy for more than a century (Herman and Moncada, 2005), and drugs that elevate CO and H2S levels are being developed (Li et al, 2009). Recent research has focused on the design of novel H2S donors several of which were proven to provide cardioprotective effects, even though the underlying mechanisms remained elusive (Zhao et al, 2015)
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