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 Ca2+-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-mu-M) nor an inhibitor of small conductance Ca2+-activated K+ channels (apamin; 0.1-mu-M) 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.