1. The effects of ouabain (1 nM-100 microM) on the membrane properties of rabbit visceral primary afferent neurones (nodose ganglion cells) were studied with intracellular recordings and voltage-clamp techniques in vitro. 2. Ouabain (greater than or equal to 1 microM) often produced a membrane hyperpolarization associated with a fall of membrane resistance in type C neurones. The ouabain-induced hyperpolarization reversed in polarity at about -90 mV. These suggest that the ouabain-induced hyperpolarization is due to an increase in potassium conductance. 3. Both the peak amplitude and the duration of the after-hyperpolarization following an action potential were reversibly increased with increasing concentration of ouabain. In tetraethylammonium (TEA, 10-20 mM) and tetrodotoxin (TTX, 1-10 microM), the duration of both the calcium-dependent action potential and the after-hyperpolarization following the action potential was prolonged by ouabain (greater than or equal to 10 nM). 4. A depolarizing command pulse evoked a slow outward current in TEA (10-20 mM) and TTX (1-10 microM). This was increased in amplitude and prolonged in duration by ouabain (100 nM-1 microM). Such augmentation of the slow outward current by ouabain was usually associated with an increase in a slow inward current during the period of the depolarizing command pulse. 5. An outward current produced by the calcium ionophore A23187 was reversibly augmented by ouabain (greater than or equal to 10 nM). 6. An outward current caused by exchanging a potassium-free superfusion solution for one containing 4.7 or 10 mM-potassium was completely abolished by ouabain (greater than or equal to 10 nM). 7. The hyperpolarization elicited by intracellular injection of calcium was reversibly prolonged by either ouabain (1 microM) or caffeine (10 nM). 8. These results suggest that ouabain augments the after-hyperpolarization both by an increase in calcium influx across the cellular membrane and by an increase in intracellular calcium concentration.
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http://dx.doi.org/10.1113/jphysiol.1987.sp016675 | DOI Listing |
Eur J Neurosci
December 2024
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas, USA.
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Institute for Health and Sport, Victoria University, Melbourne, Australia.
J Neurophysiol
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Department of Biology, Queen's University, Kingston, Ontario, Canada.
Spreading depolarization (SD) describes the near-complete depolarization of central nervous system (CNS) neural cells as a consequence of chemical, electrical, or metabolic perturbations. It is well established as the central mechanism underlying insect coma and various mammalian neurological dysfunctions. Despite significant progress in our understanding, the question remains: which cation channel, if any, generates SD in the CNS? Previously, we speculated that the sodium-potassium ATPase (NKA) might function as a large-conductance ion channel to initiate SD in insects, potentially mediated by a palytoxin (PLTX)-like endogenous activator.
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Laboratory of Enzymology and Cell Signaling, Department of Cellular and Molecular Biology, Institute of Biology, Universidade Federal Fluminense, Niterói, RJ, 24020-141, Brazil. Electronic address:
Bipolar Disorder (BD) is a psychiatric disorder marked by mood swings between manic and depressive episodes. The reduction in the Na,K-ATPase (NKA) enzyme activity and the inability of individuals with BD to produce endogenous ouabain (EO) at sufficient levels to stimulate this enzyme during stressful events are factors proposed for BD etiology. According to these hypotheses, reduction in NKA activity would result in altered neuronal resting potential, leading to BD symptoms.
View Article and Find Full Text PDFJ Recept Signal Transduct Res
April 2024
Department of Pharmacology & Toxicology, College of Veterinary Science and Animal Husbandry, Orissa University of Agriculture and Technology, Bhubaneswar, India.
Preeclampsia, a gestational associated hypertension, has been reported in 6-8% of pregnant women worldwide leading to premature delivery and low birth weight of newborn due to reduced blood flow to placenta. Although several vasodilators (Methyl dopa, hydralazine, β-blockers and diuretics) are currently in use to treat preeclampsia, still there is a search for safer drugs with better efficacy. Lately, antihypertensive vasodilators from natural sources are gaining importance in treating preeclampsia.
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