The Journal of Neuroscience, August 15, 1998, 18(16):6254-6260
Regulation of M-Type Potassium Current by Intracellular
Nucleotide Phosphates
Mark A.
Simmons and
Carla R.
Schneider
The Neuropharmacology Laboratory, Department of Pharmacology,
Marshall University, Huntington, West Virginia 25704-9388
The effects of intracellular application of various concentrations
of adenine nucleoside phosphates and nucleotide analogs on the M-type K
current (IM) of single neurons
isolated from sympathetic ganglia were studied. With 1 mM
MgATP intracellularly IM decreased to 25%
of its initial level 39 min after the start of whole-cell recording. In
the absence of ATP the current decreased more rapidly. Addition of
glucose and pyruvate extracellularly was equivalent to adding 1 mM MgATP intracellularly. AMP-PNP, a nonhydrolyzable ATP
analog, at a concentration of 1 or 3 mM was unable to
maintain IM in the absence of ATP. When ATP
and AMP-PNP were combined in the pipette, however, the maintenance of
IM was prolonged. A series of nucleotides
and analogs have been combined with ATP to test for their ability to
maintain IM and to alter calcineurin
phosphatase activity. There was a positive correlation between the
ability of a nucleotide to prevent the rundown of
IM and its ability to inhibit calcineurin
phosphatase activity. These findings show that the amplitude of
IM is dually regulated by cellular levels of
adenine nucleotide diphosphates and triphosphates. A hydrolyzable form
of ATP is necessary to maintain the M current. The maintenance of
IM is further enhanced by the simultaneous
presence of ADP or other adenine nucleotides that alter calcineurin
activity, but not by higher concentrations of ATP alone. These results
are consistent with regulation of IM by
phosphorylation events that maintain IM and
dephosphorylation events that lead to current rundown.
Key words:
ATP; M-current; sympathetic neuron; potassium current; calcineurin; nucleotide phosphates; phosphorylation; phosphatase
Copyright © 1998 Society for Neuroscience 0270-6474/98/18166254-07$05.00/0
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