Bradykinin and ATP accelerate Ca(2+) efflux from rat sensory neurons via protein kinase C and the plasma membrane Ca(2+) pump isoform 4

• Published in: Neuron (Cambridge, Mass.) Vol. 33; no. 1; pp. 113 - 122
• Main Authors: Usachev, Yuriy M, DeMarco, Steven J, Campbell, Colin, Strehler, Emanuel E, Thayer, Stanley A
• Format: Journal Article
• Language: English
• Published: United States 03-01-2002
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - metabolism; Adenosine Triphosphate - pharmacology; Animals; Bradykinin - metabolism; Bradykinin - pharmacology; Calcium - metabolism; Calcium Signaling - drug effects; Calcium Signaling - physiology; Calcium-Transporting ATPases - drug effects; Calcium-Transporting ATPases - metabolism; Cation Transport Proteins; Cell Membrane - drug effects; Cell Membrane - metabolism; Cells, Cultured; Enzyme Inhibitors - pharmacology; Ganglia, Spinal - cytology; Ganglia, Spinal - drug effects; Ganglia, Spinal - enzymology; Green Fluorescent Proteins; Immunohistochemistry; Indicators and Reagents - metabolism; Luminescent Proteins - genetics; Neurons, Afferent - cytology; Neurons, Afferent - drug effects; Neurons, Afferent - enzymology; Plasma Membrane Calcium-Transporting ATPases; Protein Isoforms - drug effects; Protein Isoforms - metabolism; Protein Kinase C - drug effects; Protein Kinase C - metabolism; Rats; Receptors, Purinergic - drug effects; Receptors, Purinergic - metabolism; Signal Transduction - drug effects; Signal Transduction - physiology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology
• ISSN: 0896-6273
• DOI: 10.1016/S0896-6273(01)00557-8

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