Norepinephrine selectively reduces slow Ca2+- and Na+-mediated K+ currents in cat neocortical neurons

Robert Foehring, P. C. Schwindt, W. E. Crill

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

The effects of norepinephrine (NE) and related agonists and antagonists were examined on large neurons from layer V of cat sensorimotor cortex ('Betz cells') were examined in a brain slice preparation using intracellular recording, constant current stimulation and single microelectrode voltage clamp. Application of NE (0.1-100 μM) usually caused a small depolarization from resting potential; hyperpolarizations were rare. Application of NE reversibly reduced rheobase and both the Ca2+- and Na+-dependent portions of the slow afterhyperpolarization (sAHP) that followed sustained firing evoked by constant current injection. The faster Ca2+-dependent medium afterhyperpolarization (mAHP), the fast afterhyperpolarization (fAHP), the action potential, and input resistance were unaffected. The changes in excitability produced by NE application were most apparent during prolonged stimulation. The cells exhibited steady repetitive firing to currents that were formerly ineffective. The slow phase of spike frequency adaptation was reduced selectively and less habituation occurred during repeated long-lasting stimuli. The relation between firing rate and injected current became steeper if firing rate was averaged over several hundred milliseconds. During voltage clamp in TTX, NE application selectively reduced the slow component of Ca2+-mediated K+ current. The faster Ca2+-mediated K+ current was unaffected, as were two voltage-dependent, transient K+ currents, the anomalous rectifier and leakage conductance measured at resting potential. Depolarizing voltage steps in the presence of Cd2+ revealed an apparent time- and voltage-dependent increase of the persistent Na+ current after NE application. The voltage-clamp results suggested ionic mechanisms for all effects seen during constant current stimulation except the depolarization from resting potential. The latter was insensitive to Cd2+ and TTX and occurred without a detectable change in membrane conductance. NE application did not alter Ca2+ spikes evoked in the presence of TTX and 10 mM TEA. Inward Ca2+ currents examined during voltage clamp in TTX (with K+ currents reduced) became slightly larger after NE application. We conclude that NEs reduction of the slow Ca2+-mediated K+ current is not caused by reduction of Ca2+ influx. Effects on membrane potential, rheobase, and the sAHP were mimicked by the β-adrenergic agonist isoproterenol, but not by the α-adrenergic agonists clonidine or phenylephrine at higher concentrations. Reduction of the sAHP was prevented by the β-antagonists timolol or propranolol and the β-1 antagonist atenolol, but not by the β-2 antagonist butoxamine at the same concentration nor by the 2a-antagonist phentolamine at high concentrations. NE's reduction of the slow Ca2+- and Na+-dependent K+ currents is likely mediated by β-1 receptors. We conclude that NE acts primarily as an excitatory neuromodulator of Betz cells in vitro. Its effects are most pronounced during sufficiently large and long depolarization. By its selective reduction of the slow K+ currents, it lessens the slow decrease of excitability that normally accompanies prolonged repetitive firing.

Original languageEnglish (US)
Pages (from-to)245-256
Number of pages12
JournalJournal of Neurophysiology
Volume61
Issue number2
DOIs
StatePublished - Jan 1 1989
Externally publishedYes

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Norepinephrine
Cats
Neurons
Membrane Potentials
Adrenergic Agonists
Butoxamine
Timolol
Atenolol
Potassium Chloride
Phentolamine
Clonidine
Microelectrodes
Phenylephrine
Isoproterenol
Propranolol
Action Potentials
Neurotransmitter Agents
Injections
Membranes
Brain

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

Cite this

Norepinephrine selectively reduces slow Ca2+- and Na+-mediated K+ currents in cat neocortical neurons. / Foehring, Robert; Schwindt, P. C.; Crill, W. E.

In: Journal of Neurophysiology, Vol. 61, No. 2, 01.01.1989, p. 245-256.

Research output: Contribution to journalArticle

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