Dominguez-Rodriguez Manuel, Drobny Helmut, Boehm Stefan, Salzer Isabella
Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of ViennaVienna, Austria.
Front Pharmacol. 2017 Aug 4;8:522. doi: 10.3389/fphar.2017.00522. eCollection 2017.
HS is well-known as hypotensive agent, whether it is synthetized endogenously or administered systemically. Moreover, the HS 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, HS 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 HS donor as well as HS itself caused membrane hyperpolarization and decreased action potential firing in response to current injection. Submillimolar NaHS concentrations did not affect currents through K7 channels, but did evoke currents through K channels. Similarly to NaHS, the K channel activator diazoxide led to hyperpolarization and decreased membrane excitability; the effects of both, NaHS and diazoxide, were prevented by the K channel blocker tolbutamide. At postganglionic sympathetic nerve terminals, HS and NaHS enhanced noradrenaline release due to a direct action at the level of vesicle exocytosis. Taken together, HS 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 K channel gating, this channel family is hereby established as another previously unrecognized determinant in the function of sympathetic ganglia.
硫化氢作为一种降压剂广为人知，无论它是内源性合成还是全身给药。此外，硫化氢供体硫氢化钠已被证明可抑制由节前交感神经纤维刺激引发的升压反应。与后一结果相反，有报道称硫氢化钠可促进交感神经节内的信号传递。为了解决这一矛盾，将硫化氢和硫氢化钠应用于解离的交感神经节原代培养物，以揭示这种气体递质可能如何作用于此类神经元的不同亚细胞区室。在神经节神经元的树突体区域，硫氢化钠通过突触前作用位点提高了胆碱能微小突触后电流的频率，但不影响其幅度。此外，硫化氢供体以及硫化氢本身都会引起膜超极化，并减少电流注入时的动作电位发放。亚毫摩尔浓度的硫氢化钠不会影响通过K7通道的电流，但会引发通过K通道的电流。与硫氢化钠类似，K通道激活剂二氮嗪也会导致超极化并降低膜兴奋性；硫氢化钠和二氮嗪的作用均被K通道阻滞剂甲苯磺丁脲所阻断。在节后交感神经末梢，硫化氢和硫氢化钠通过对囊泡胞吐水平的直接作用增强去甲肾上腺素释放。综上所述，硫化氢可能促进交感神经节内和交感效应器连接处的递质释放，但会导致神经节神经元超极化并降低膜兴奋性。由于后一种作用是由于K通道门控引起的，因此该通道家族在此被确立为交感神经节功能中另一个先前未被认识的决定因素。
