Bradykinin and ATP accelerate Ca2+ efflux from rat sensory neurons via protein kinase C and the plasma membrane Ca2+ pump isoform 4

Yuriy M. Usachev, Steven J. DeMarco, Colin Campbell, Emanuel E. Strehler, Stanley A. Thayer

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

Modulation of Ca2+ channels by neurotransmitters provides critical control of neuronal excitability and synaptic strength. Little is known about regulation of the Ca2+ efflux pathways that counterbalance Ca2+ influx in neurons. We demonstrate that bradykinin and ATP significantly facilitate removal of action potential-induced Ca2+ loads by stimulating plasma membrane Ca2+-ATPases (PMCAs) in rat sensory neurons. This effect was mimicked in the soma and axonal varicosities by phorbol esters and was blocked by antagonists of protein kinase C (PKC). Reduced expression of PMCA isoform 4 abolished, and overexpression of isoform 4b enhanced, PKC-dependent facilitation of Ca2+ efflux. This acceleration of PMCA4 underlies the shortening of the action potential afterhyperpolarization produced by activation of bradykinin and purinergic receptors. Thus, isoform-specific modulation of PMCA-mediated Ca2+ efflux represents a novel mechanism to control excitability in sensory neurons.

Original languageEnglish (US)
Pages (from-to)113-122
Number of pages10
JournalNeuron
Volume33
Issue number1
DOIs
StatePublished - Jan 3 2002

Bibliographical note

Funding Information:
We thank Kevin Wickman and Ed McClesky for comments on the manuscript; Ali Khammanivong, Wenna Lin, and Kyle Baron for excellent technical assistance; and Adelaida Filoteo and John Penniston for the generous gift of anti-PMCA antibodies. The National Science Foundation (IBN0110409) and the National Institutes of Health (AG16678, DA07304, DA09293, DC04200, GM58710) supported this work.

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