Modulation of calcium channels by norepinephrine in internally dialyzed avian sensory neurons

P. Forscher, G. S. Oxford

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

Modulation of voltage-dependent Ca channels by norepinephrine (NE) was studied in chick dorsal root ganglion cells using the whole-cell configuration of the patch-clamp technique. Cells dialyzed with K+ and 2-10 mM EGTA exhibited Ca action potentials that were reversibly decreased in duration and amplitude by NE. Ca channel currents were isolated from other channel contributions by using: (a) tetrodotoxin (TTX) to block g(Na), (b) internal K channel impermeant ions (Cs or Na/N-methylglucamine mixtures) as K substitutes, (c) external tetraethylammonium (TEA) to block K channels, (d) internal EGTA to reduce possible current contribution from Ca-activated channels. A marked decline (rundown) of Ca conductance was observed during continual dialysis, which obscured reversible NE effects. The addition of 2-5 mM MgATP to the intracellular solutions greatly retarded Ca channel rundown and permitted a clear assessment of modulatory drug effects. The inclusion of an intracellular creatine phosphate/creatine phosphokinase nucleotide regeneration system further stabilized Ca channels, which permitted recording of Ca currents for up to 3 h. NE reversibly decreased both steady state Ca currents and Ca tail currents in Cs/EGTA/MgATP-dialyzed cells. A possible role of several putative intracellular second messengers in NE receptor-Ca channel coupling was investigated. Cyclic AMP or cyclic GMP added to the intracellular solutions at concentrations several orders of magnitude higher than the K(d) for activation of cyclic nucleotide-dependent protein kinases did not block or mask the expression of the NE-mediated decrease in g(Ca). Addition of internal EGTA to a final concentration of 10 mM also did not affect the expression of the NE response. These results suggest that neither cyclic AMP nor cyclic GMP nor Ca is acting a a second messenger coupling the NE receptor to the down-modulated Ca channel population.

Original languageEnglish (US)
Pages (from-to)743-763
Number of pages21
JournalJournal of General Physiology
Volume85
Issue number5
StatePublished - 1985
Externally publishedYes

Fingerprint

Sensory Receptor Cells
Calcium Channels
Norepinephrine
Egtazic Acid
Cyclic GMP
Second Messenger Systems
Cyclic AMP
Adrenergic Receptors
Adenosine Triphosphate
Meglumine
Tetraethylammonium
Phosphocreatine
Cyclic Nucleotides
Tetrodotoxin
Spinal Ganglia
Patch-Clamp Techniques
Creatine Kinase
Masks
Ion Channels
Protein Kinases

ASJC Scopus subject areas

  • Physiology

Cite this

Modulation of calcium channels by norepinephrine in internally dialyzed avian sensory neurons. / Forscher, P.; Oxford, G. S.

In: Journal of General Physiology, Vol. 85, No. 5, 1985, p. 743-763.

Research output: Contribution to journalArticle

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