Calcium-activated potassium channels mediate prejunctional inhibition of peripheral sensory nerves.
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.
Stretton
D
D
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
Miura
M
M
Belvisi
M G
MG
Barnes
P J
PJ
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001980:Bronchi / Q000294:innervation*; D016084:Bronchoconstriction / Q000187:drug effects; D002118:Calcium / Q000502:physiology*; D027682:Cation Transport Proteins; D018999:Charybdotoxin; D003000:Clonidine / Q000494:pharmacology; D006224:Cricetinae; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008297:Male; D009433:Neural Inhibition; D009475:Neurons, Afferent / Q000502:physiology*; D009478:Neuropeptide Y / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D011759:Pyrrolidines / Q000494:pharmacology; D012604:Scorpion Venoms / Q000494:pharmacology*
D027682:Cation Transport Proteins; D004745:Enkephalins; D009478:Neuropeptide Y; D015221:Potassium Channels; D011759:Pyrrolidines; D012604:Scorpion Venoms; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D018999:Charybdotoxin; D001030:Apamin; C045506:BRL 31660; D000251:Adenosine Triphosphatases; C022761:potassium transporting ATPase; D003000:Clonidine; D005905:Glyburide; D002118:Calcium