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.
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
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D
Stretton
M
M
Miura
M G
MG
Belvisi
P J
PJ
Barnes
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