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Phosphorylase a and Labile Metabolites During Anoxia: Correlation to Membrane Fluxes of K + and Ca 2+
Author(s) -
Folbergrová Jaroslava,
Minamisawa Hiroaki,
Ekholm Anders,
Siesjö Bo K.
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb04957.x
Subject(s) - depolarization , chemistry , extracellular , glycogenolysis , calcium , glycogen phosphorylase , cytosol , biophysics , ischemia , membrane potential , conductance , biochemistry , metabolism , medicine , enzyme , biology , mathematics , organic chemistry , combinatorics
The objective of the present study was to explore mechanisms responsible for activation of ion conductances in the initial phases of brain ischemia, particularly for the early release of K + that precedes massive cell depolarization, and rapid downhill fluxes of K + , Na + , Cl − , and Ca 2+ . As it has been speculated that a K + conductance can be activated either by an increase in the free cytosolic calcium concentration (Ca 2+ i ) or by a fall in ATP concentration, the question arises whether the early increase in extracellular K + concentration (K + e ) is preceded by a rise in Ca 2+ i and/or a fall in ATP content. In the present experiments, ischemia was induced in rats by cardiac arrest, the time courses of the rise in K + e and cellular depolarization were determined by microelectrodes, and the tissue was frozen in situ through the exposed dura for measurements of levels of labile metabolites, including adenine nucleotides and cyclic AMP (cAMP), after ischemic periods of 15, 30, 60, and 120 s. Conversion of phosphorylase b to a was assessed, because it depends, among other things, on changes in Ca 2+ i . The K + e value rose within a few seconds following induction of ischemia, but massive depolarization (which is accompanied by influx of calcium) did not occur until after ∼65 s. Activation of phosphorylase was observed already after 15 s and before glycogenolysis had begun. At that time, 3′,5′‐cAMP concentrations were unchanged, and total 5′‐AMP concentrations were only moderately increased. The results demonstrate that a K + conductance is activated at a time when the overall ATP concentration remains at 95% of control values. If major compartmentation can be excluded, the results fail to demonstrate that an ATP‐activated K + conductance is involved. In view of the early activation of phosphorylase, one may speculate that the triggering event is a rise in Ca 2+ i .