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Differential effects of protein kinase C activation on 5-HT1A receptor coupling to Ca2+ and K+ currents in rat

Y Chen1, N J Penington

  • 1Department of Pharmacology, State University of New York, Health Science Center at Brooklyn 11203-2098, USA.

The Journal of Physiology
|October 1, 1996
PubMed

Insights

Protein kinase C (PKC) activation selectively impairs 5-HT1A receptor signaling, reducing calcium (Ca2+) current inhibition while leaving 5-HT-induced potassium (K+) currents unaffected in rat neurons.

Area of Science:

  • Neuropharmacology
  • Molecular Neuroscience
  • Cellular Signaling

Background:

  • Serotonin 5-HT1A receptors are crucial in regulating neuronal excitability.
  • Protein kinase C (PKC) is implicated in modulating receptor-G protein interactions.
  • Understanding PKC's role in 5-HT1A receptor signaling is key to deciphering neuronal control mechanisms.

Purpose of the Study:

  • To investigate the impact of PKC activation on 5-HT1A receptor-mediated inhibition of Ca2+ currents.
  • To examine the effect of PKC activation on 5-HT-induced K+ currents (IK,5-HT).
  • To elucidate the specific branch of the 5-HT1A receptor transduction pathway affected by PKC.

Main Methods:

  • Utilized acutely isolated adult rat dorsal raphe neurons.
  • Applied phorbol ester 4 beta-phorbol 12-myristate, 13-acetate (PMA) to activate PKC.
  • Administered 5-hydroxytryptamine (5-HT) to activate 5-HT1A receptors.
  • Used inactive phorbol ester 4 alpha-phorbol and kinase inhibitor staurosporine (ST) as controls.

Main Results:

  • PKC activation by PMA partially uncoupled 5-HT1A receptors from Ca2+ current inhibition (52% to 30%).
  • The inhibitory effect of 5-HT on Ca2+ current was irreversible after PMA treatment.
  • PKC activation did not significantly affect 5-HT-induced K+ currents (IK,5-HT).
  • Staurosporine partially prevented or reversed PMA's effect on Ca2+ current inhibition.

Conclusions:

  • PKC activation selectively inhibits the 5-HT1A receptor-mediated suppression of Ca2+ influx.
  • The activation of IK,5-HT by 5-HT1A receptors is not affected by PKC.
  • PKC acts on a specific transductional branch of the 5-HT1A receptor, impacting Ca2+ channels but not K+ channels.

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