Abstract
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.
Publication types
-
Research Support, U.S. Gov't, Non-P.H.S.
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
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
Substances
-
Cation Transport Proteins
-
Enzyme Inhibitors
-
Indicators and Reagents
-
Luminescent Proteins
-
Protein Isoforms
-
Receptors, Purinergic
-
Green Fluorescent Proteins
-
Adenosine Triphosphate
-
Protein Kinase C
-
Plasma Membrane Calcium-Transporting ATPases
-
Calcium-Transporting ATPases
-
Bradykinin
-
Calcium