Objective: To investigate the effects of endogenous and exogenous hydrogen sulfide (H(2)S) on the K(ATP) current in isolated rat ventricular myocytes.
Methods: Ventricular myocytes were isolated from rat heart by modified Langendorff perfusion with collagenase. K(ATP) current of single rat ventricular myocytes was recorded by whole-cell patch-clamp technique.
Results: The density of K(ATP) current was significantly reduced by 200 micromol/L DL-propargylglycine (PPG, an irreversible inhibitor of the H(2)S) [(5.3258 +/- 0.7556) pA/pF vs. (3.7856 +/- 0.4312) pA/pF, P < 0.01] in a time-dependent way. The density of K(ATP) current could be significantly increased by NaHS (a H(2)S donor, 9.375, 18.75, 37.5, 75, 150 micromol/L) in a concentration-dependent manner [(6.6310 +/- 0.6092) pA/pF vs. (9.0949 +/- 1.0259) pA/pF at 150 micromol/L, P < 0.01].
Conclusion: Both endogenous and exogenous H(2)S could open K(ATP) channels and enhance the K(ATP) current in rat ventricular myocytes.
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Front Immunol
December 2024
Department of Pathology, NYU Grossman School of Medicine, New York, NY, United States.
Introduction: Involved in immunity and reproduction, natural killer (NK) cells offer opportunities to develop new immunotherapies to treat infections and cancer or to alleviate pregnancy complications. Most current strategies use cytokines or antibodies to enhance NK-cell function, but none use ion channel modulators, which are widely used in clinical practice to treat hypertension, diabetes, epilepsy, and other conditions. Little is known about ion channels in NK cells.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201.
The brain has evolved mechanisms to dynamically modify blood flow, enabling the timely delivery of energy substrates in response to local metabolic demands. Several such neurovascular coupling (NVC) mechanisms have been identified, but the vascular signal transduction and transmission mechanisms that enable dilation of penetrating arterioles (PAs) remote from sites of increased neuronal activity are unclear. Given the exponential relationship between vessel diameter and blood flow, tight control of arteriole membrane potential and diameter is a crucial aspect of NVC.
View Article and Find Full Text PDFNeuroscience
January 2025
Laboratory of Neurophysiology and Synapse, Department of Physiology, School of Medicine of Ribeirão Preto, Ribeirão Preto, SP, Brazil. Electronic address:
Cartwheel (CW) neurons are glycinergic interneurons in the dorsal cochlear nucleus (DCN) that exhibit spontaneous firing, resulting in potent tonic inhibition of fusiform neurons. CW neurons expressing open ATP-sensitive potassium (K) channels do not fire spontaneously, and activation of K channels halts spontaneous firing in these neurons. However, the conditions that regulate K channel opening in CW neurons remain unknown.
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December 2024
Orthopedic Microsurgical Reconstruction Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China. Electronic address:
The clinical management of neuropathic pain (NP) remains a significant challenge, as current pharmacological treatments do not fully meet clinical needs. Nicorandil, a potassium ATP channel agonist widely used in cardiovascular medicine, has recently been shown to have significant potential for analgesia. This study aimed to investigate the effects and mechanisms of nicorandil in a chronic constriction injury (CCI) mouse model.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, OR 97239, USA.
Pancreatic K channel trafficking defects underlie congenital hyperinsulinism (CHI) cases unresponsive to the K channel opener diazoxide, the mainstay medical therapy for CHI. Current clinically used K channel inhibitors have been shown to act as pharmacochaperones and restore surface expression of trafficking mutants; however, their therapeutic utility for K trafficking impaired CHI is hindered by high-affinity binding, which limits functional recovery of rescued channels. Recent structural studies of K channels employing cryo-electron microscopy (cryoEM) have revealed a promiscuous pocket where several known K pharmacochaperones bind.
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