Bradykinin and ATP Accelerate Ca super(2+) Efflux from Rat Sensory Neurons via Protein Kinase C and the Plasma Membrane Ca super(2+) Pump Isoform 4

• Published in: Neuron (Cambridge, Mass.) Vol. 33; no. 1; pp. 113 - 122
• Main Authors: Usachev, Y M, DeMarco, S J, Campbell, C, Strehler, EE, Thayer, SA
• Format: Journal Article
• Language: English
• Published: 01-01-2002
• ISSN: 0896-6273

Modulation of Ca super(2+) channels by neurotransmitters provides critical control of neuronal excitability and synaptic strength. Little is known about regulation of the Ca super(2+) efflux pathways that counterbalance Ca super(2+) influx in neurons. We demonstrate that bradykinin and ATP significantly facilitate removal of action potential-induced Ca super(2+) loads by stimulating plasma membrane Ca super(2+)-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 Ca super(2+) 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 Ca super(2+) efflux represents a novel mechanism to control excitability in sensory neurons.