Calcium-activated potassium channels mediate prejunctional inhibition of peripheral sensory nerves

Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1325-9. doi: 10.1073/pnas.89.4.1325.

Abstract

Activation of several receptors, including mu-opioid, alpha 2-adrenergic, and neuropeptide Y receptors, inhibits excitatory nonadrenergic noncholinergic (NANC) neural responses in airways, which were mediated by the release of peptides from capsaicin-sensitive sensory nerves. This raises the possibility of a common inhibitory mechanism, which may be related to an increase in K+ conductance in sensory nerves. To examine this hypothesis, we have studied whether K(+)-channel blockers inhibit the effects of neuromodulators of sensory nerves in guinea pig bronchi by using selective K(+)-channel blockers. Charybdotoxin (ChTX; 10 nM), which blocks large conductance Ca(2+)-activated K(+)-channel function, completely blocked and reversed the inhibitory effects of a mu-opioid agonist, neuropeptide Y, and an alpha 2-adrenoceptor agonist on excitatory NANC responses. Neither inhibitors of ATP-sensitive K+ channels (BRL 31660 or glibenclamide, both at 10 microM) nor an inhibitor of small conductance Ca(2+)-activated K+ channels (apamin; 0.1 microM) were effective. This suggests that ChTX-sensitive K(+)-channel activation may be a common mechanism for the prejunctional modulation of sensory nerves in airways. This may have important implications for the control of neurogenic inflammation.

MeSH terms

  • Adenosine Triphosphatases / antagonists & inhibitors
  • Animals
  • Apamin / pharmacology
  • Bronchi / innervation*
  • Bronchoconstriction / drug effects
  • Calcium / physiology*
  • Cation Transport Proteins
  • Charybdotoxin
  • Clonidine / pharmacology
  • Cricetinae
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalins / pharmacology
  • Glyburide / pharmacology
  • In Vitro Techniques
  • Ion Channel Gating
  • Male
  • Neural Inhibition*
  • Neurons, Afferent / physiology*
  • Neuropeptide Y / pharmacology
  • Potassium Channels / physiology*
  • Pyrrolidines / pharmacology
  • Scorpion Venoms / pharmacology*

Substances

  • Cation Transport Proteins
  • Enkephalins
  • Neuropeptide Y
  • Potassium Channels
  • Pyrrolidines
  • Scorpion Venoms
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Charybdotoxin
  • Apamin
  • BRL 31660
  • Adenosine Triphosphatases
  • potassium transporting ATPase
  • Clonidine
  • Glyburide
  • Calcium