Work

Depolarization of Rat Brain Synaptosomes Increases Phosphorylation of Voltage-sensitive Sodium Channels

Year: 1997

Type: article

Abstract: Depolarization of rat brain synaptosomes causes an increase in phosphorylation of serine residues 573, 610, 623, and 687 on voltage-sensitive sodium channels. Although these sites have been shown to be phosphorylated by cAMP-dependent protein kinase in vitro and in situ, the depolarization-induced increase in their state of phosphorylation is not due to increased cAMP-dependent protein kinase activity, but requires calcium influx and protein kinase C. Since phosphorylation at this cluster of sites inhibits sodium current and would decrease neuronal excitability, this may be an important negative feedback mechanism whereby calcium influx during prolonged or repetitive depolarization can attenuate neuronal excitability and prevent further calcium accumulation. Phosphorylation of purified channels by protein kinase C decreases dephosphorylation of cAMP-dependent phosphorylation sites by purified calcineurin or protein phosphatase 2A. This suggests that one mechanism by which protein kinase C may increase phosphorylation of cAMP-dependent phosphorylation sites in sodium channels is to inhibit their dephosphorylation. This represents an important new mechanism for convergent regulation of an ion channel by two distinct signal transduction pathways.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.272.27.16978

Authors: Tamara Kondratyuk, Sandra Rossie

Institution: Purdue University West Lafayette

Language: English

Topic: Ion channel regulation and function

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $3,430

Funder: National Institute of Neurological Disorders and Stroke