title: Protease-activated receptor-2 inhibits BK channel activity in bronchopulmonary sensory neurons.
abstract: Activation of protease-activated receptor-2 (PAR2) contributes to airway inflammation and airway hypersensitivity, the hallmark features of allergic asthma; and a neurogenic mechanism involving hypersensitivity of bronchopulmonary sensory nerves has been indicated. Large-conductance Ca(2+)-activated potassium (BK) channels are known to play an important role in shaping neuronal excitability. The aim of this study was to investigate the potential regulation of BK channel activities by PAR2 activation in vagal bronchopulmonary sensory neurons. Our results showed that pretreatment with PAR2-activating peptide (PAR2-AP; 100μM, 120s), but not its control peptide PAR2-RP, significantly reduced BK current density in these neurons. Inhibition of phospholipase C, PKC, PKA or MEK/ERK signaling pathway did not prevent the suppression of BK current by PAR2 activation; whereas intracellular application of Ca(2+) chelator BAPTA-AM completely abolished the PAR2 regulation of BK current. In addition, our results demonstrated that activation of PAR2 increased excitability of bronchopulmonary sensory neurons, in a similar manner as displayed by a direct BK channel blockade. In summary, our data suggest that suppression of BK channel activity contributes to PAR2 activation-induced hyperexcitability of vagal bronchopulmonary sensory neurons.
authors.affiliation: Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College Street, Macon, GA 31207, USA.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Moss
authors.affiliation: Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College Street, Macon, GA 31207, USA.
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Gilbert
authors.affiliation: Department of Family Medicine, Mercer University School of Medicine and Medical Center of Central Georgia, Macon, GA 31207, USA.
authors.forename: Sabry A
authors.initials: SA
authors.lastname: Gabriel
authors.affiliation: Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College Street, Macon, GA 31207, USA.
authors.forename: Qihai
authors.initials: Q
authors.lastname: Gu
mesh_terms: D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000294:innervation / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000294:innervation / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D044464:Receptor, PAR-2 / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C487404:2-furoyl-LIGRLO-amide; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009842:Oligopeptides; D044464:Receptor, PAR-2; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases
keywords: Airway hyperresponsiveness; Bronchopulmonary sensory neuron; Large-conductance Ca(2+)-activated potassium channel; Neurogenic inflammation; Protease-activated receptor-2