Phorbol ester-induced inhibition of potassium currents in rat sensory neurons requires voltage-dependent entry of calcium

Yi Hong Zhang, J. L. Kenyon, Grant Nicol

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The whole cell patch-clamp technique was used to examine the effects of protein kinase C (PKC) activation (via the phorbol ester, phorbol 12,13 dibutyrate, PDBu) on the modulation of potassium currents (IΚ) in cultured capsaicin-sensitive neurons isolated from dorsal root ganglia from embryonic rat pups and grown in culture. PDBu, in a concentration- and time-dependent manner, reduced IΚ measured at +60 mV by ∼30% if the holding potential (Vh) was -20 or -47 mV but had no effect if Vh was -80 mV. The PDBu-induced inhibition of IΚ was blocked by pretreatment with the PKC inhibitor bisindolylmaleimide I and IΚ was unaffected by 4-α phorbol, indicating that the suppression of IΚ was mediated by PKC. The inhibition of IΚ by 100 nM PDBu at a Vh of -50 mV was reversed over several minutes if Vh was changed to -80 mV. In addition, intracellular perfusion with 5 mM bis-(o-aminophenoxy)-N,N,N′,N′-tetraacetic acid (BAPTA) or pretreatment with ω-conotoxin GVIA or Cd2+-Ringer, but not nifedipine, prevented the PDBu-induced suppression of IΚ at -50 mV, suggesting that a voltage-dependent influx of calcium through N-type calcium channels was necessary for the activation of PKC. The potassium channel blockers tetraethylammonium (TEA, 10 mM) and 4-aminopyridine (4-AP, 3 mM and 30 μM) reduced IΚ, but only TEA attenuated the ability of PDBu to further inhibit the current, suggesting that the IΚ modified by PDBu was sensitive to TEA. Interestingly, in the presence of 3 mM or 30 μM 4-AP, 100 nM PDBu inhibited 1Κ when Vh was -80 mV. Thus 4-AP promotes the capacity of PDBu to reduce IΚ at -80 mV. We find that activation of PKC inhibits IΚ in rat sensory neurons and that voltage-dependent calcium entry is necessary for the development and maintenance of this inhibition.

Original languageEnglish
Pages (from-to)362-373
Number of pages12
JournalJournal of Neurophysiology
Volume85
Issue number1
StatePublished - 2001

Fingerprint

Phorbol Esters
Sensory Receptor Cells
Protein Kinase C
Potassium
Calcium
N-Type Calcium Channels
Conotoxins
Potassium Channel Blockers
Phorbol 12,13-Dibutyrate
4-Aminopyridine
Tetraethylammonium
Protein C Inhibitor
Capsaicin
Spinal Ganglia
Patch-Clamp Techniques
Nifedipine
Protein Kinase Inhibitors
Perfusion
Maintenance
Neurons

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Phorbol ester-induced inhibition of potassium currents in rat sensory neurons requires voltage-dependent entry of calcium. / Zhang, Yi Hong; Kenyon, J. L.; Nicol, Grant.

In: Journal of Neurophysiology, Vol. 85, No. 1, 2001, p. 362-373.

Research output: Contribution to journalArticle

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