The kinetics of the TTX sensitive Na+ current (INa) in the slowly adapting lobster stretch receptor neurone were investigated in sub- and near-threshold voltage regions using electrophysiological and pharmacological techniques. In dynamic conditions INa was found to display both fast and slow reactions. These were attributed to a fast Hodgkin-Huxley type of Na activation and inactivation, and a slow type of Na inactivation, respectively. In stationary conditions the voltage dependence of the slow Na inactivation was shifted in a depolarizing direction by increasing, and in a hyperpolarizing direction by decreasing the extracellular Ca++ concentration. From this finding as well as from its kinetic properties the slow Na inactivation was classified as a genuine gating process. The processes of fast Na activation and inactivation were too fast for a dynamic analysis with the recording technique available. An estimate of their stationary voltage dependence could however be obtained in a voltage range from about -80 to about -50 mV. The experimental findings were used for the formulation of a mathematical description of INa in the present preparation based on constant field and state transition theories.
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http://dx.doi.org/10.1111/j.1748-1716.1983.tb07253.x | DOI Listing |
Angew Chem Int Ed Engl
July 2024
Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, United States.
BMC Biol
April 2023
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Background: The non-neuronal retinal pigment epithelium (RPE) functions in intimate association with retinal photoreceptors, performing a multitude of tasks critical for maintaining retinal homeostasis and collaborating with retinal glial cells to provide metabolic support and ionic buffering. Accordingly, the RPE has recently been shown to display dynamic properties mediated by an array of ion channels usually more characteristic of astrocytes and excitable cells. The recent discovery of canonical voltage-activated Na channels in the RPE and their importance for phagocytosis of photoreceptor outer segments raises a question about their electrogenic function.
View Article and Find Full Text PDFJ Neurophysiol
October 2022
The Baker Laboratory of Pharmacology, Department of Pharmacology, Kirksville College of Osteopathic Medicine, A.T. Still University of Health Sciences, Kirksville, Missouri.
Skeletal muscle contraction triggers the exercise pressor reflex (EPR) to regulate the cardiovascular system response to exercise. During muscle contraction, substances are released that generate action potential activity in group III and IV afferents that mediate the EPR. Some of these substances increase afferent activity via G-protein-coupled receptor (GPCR) activation, but the mechanisms are incompletely understood.
View Article and Find Full Text PDFToxicol Sci
April 2022
Division of Toxicology, Wageningen University, 6708 WE Wageningen, The Netherlands.
In this study, the ability of a new in vitro/in silico quantitative in vitro-in vivo extrapolation (QIVIVE) methodology was assessed to predict the in vivo neurotoxicity of tetrodotoxin (TTX) in rodents. In vitro concentration-response data of TTX obtained in a multielectrode array assay with primary rat neonatal cortical cells and in an effect study with mouse neuro-2a cells were quantitatively extrapolated into in vivo dose-response data, using newly developed physiologically based kinetic (PBK) models for TTX in rats and mice. Incorporating a kidney compartment accounting for active renal excretion in the PBK models proved to be essential for its performance.
View Article and Find Full Text PDFEur J Pharmacol
November 2021
Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, 41940, Republic of Korea; Brain Science & Engineering Institute, Kyungpook National University, Daegu, 41940, Republic of Korea. Electronic address:
Propranolol, a representative adrenergic β-receptor antagonist, is widely used to prevent migraine attacks. Although propranolol is well known to inhibit tetrodotoxin-resistant (TTX-R) Na channels in cardiac myocytes, it is unclear whether the drug modulates these channels expressed in dural afferent neurons. In this study, we examined the effects of propranolol on TTX-R Na channels in medium-sized dural afferent neurons identified by the fluorescent dye DiI.
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