PATCH CLAMP STUDY OF A LARGE CONDUCTANCE, INWARD RECTIFYING, POTASSIUM CHANNEL IN CULTURED MOUSE HIPPOCAMPAL NEURONS (ION CHANNELS, NEUROPHYSIOLOGY, ELECTROPHYSIOLOGY).
Item
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Title
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PATCH CLAMP STUDY OF A LARGE CONDUCTANCE, INWARD RECTIFYING, POTASSIUM CHANNEL IN CULTURED MOUSE HIPPOCAMPAL NEURONS (ION CHANNELS, NEUROPHYSIOLOGY, ELECTROPHYSIOLOGY).
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Identifier
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AAI8708323
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identifier
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8708323
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Creator
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SULLIVAN, JOHN MICHAEL.
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Contributor
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S. A. Cohen
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Date
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1987
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biophysics, Medical
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Abstract
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Patch clamp methodology was used on primary dissociated cultures of mouse embryonic hippocampus to identify large conductance, inward rectifier (IR), potassium-selective channels. IR exhibits prominent rectification above the reversal potential which changes consistently with the external K('+) concentration (K(,o)('+)). Fast ramp voltage clamps infer that the rectification is an open channel property. Single channel (SC) I-V curves display a g(V-V(,K))-dependence with slope conductance dependent on the square root of K(,o)('+).;IR has a voltage-dependent probability of opening (Pv(o)) around resting membrane potential (RMP) and as P(,v)(o) is high at RMP, IR may contribute to the free running RMP. Depolarization increases P(,v)(o) above RMP, while hyperpolarization decreases it (e-fold/34 mV). The decrease in P(,v)(o) with hyperpolarization occurs largely from a decrease in the burst length (e-fold/44 mV). The requirement of three exponentials to fit the closed time distribution and one to fit the open times suggests that a minimum of three Markovian closed and one open state(s) are necessary to describe SC kinetics. SC gating behavior is maintained when isolated into 10 nM free calcium (Ca(,i)('2+)) but is lost at 1 nM, indicating that IR is voltage- and Ca(,i)('2+)-dependent.;Averaged SC currents from voltage ensembles display a voltage- and time-dependent partial deactivation that is faster with increasing hyperpolarization as predicted by steady-state measurements of the voltage-dependence of burst length. Ensemble averages predicted the temporal shape of the whole-cell IR currents. Both cesium and barium block the SC currents by what may be two different mechanisms.;IR serves as a RMP-active conductance. Its potential function in signal transduction is developed by analytical use of the conductance and kinetic data to predict the I-V curve at physiological K(,o)('+). This suggests that IR may function to: (1) aid in setting the RPM, (2) aid in cell repolarization after single action potentials (APs), (3) participate in attenuation of burst firing of APs, and (4) participate anomalously in the generation of prolonged depolarizations of membrane potential as K(,o)('+) accumulates in the perisomal restricted diffusional spaces in the intact hippocampus.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
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Program
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Biomedical Sciences
