Bradykinin activates airway parasympathetic ganglion neurons by inhibiting M-currents.
The action of bradykinin on neurons acutely isolated from airway parasympathetic ganglia of rats and its mechanism were investigated using the nystatin-perforated patch-clamp recording technique. Under current clamp conditions, an application of 0.1 microM bradykinin onto rat airway ganglion neurons induced a depolarization which was accompanied by the action potential firing. Bradykinin elicited inward currents with decreasing the membrane conductance when a ganglion neuron was held at a holding potential of -40 mV. The half-maximum effective concentration was 8.9 nM. The bradykinin response was mimicked by a B(2) receptor agonist, [Hyp(3)]-bradykinin, and was inhibited by HOE-140, a B(2) antagonist, suggesting the contribution of B(2) receptors. The bradykinin-induced inward current reversed at the K(+) equilibrium potential, which shifted 56.5 mV with a 10-fold change in extracellular K(+) concentration. The application of 10(-3) M Ba(2+) induced the inward current, and bradykinin failed to evoke a further inward current in the presence of Ba(2+). Bradykinin also reduced the amplitude of M-current deactivation induced by a hyperpolarizing step from a holding potential of -25 mV to -50 mV with a half-maximum effective concentration of 16 nM. Pretreatment with pertussis toxin had no effect on the bradykinin-induced inhibition of the M-current. From these results we suggest that bradykinin may be able to depolarize the airway parasympathetic ganglion neurons of rats associated with an inhibition of M-type K(+) channels through the B(2) type of bradykinin receptors.
Mochidome
T
T
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, 862-0973, Kumamoto, Japan.
Ishibashi
H
H
Takahama
K
K
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005726:Ganglia, Parasympathetic / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin / Q000819:agonists / Q000378:metabolism; D014132:Trachea / Q000294:innervation* / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D065168:Bradykinin Receptor Antagonists; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018002:Receptors, Bradykinin; D010566:Virulence Factors, Bordetella; D001464:Barium; D037342:Pertussis Toxin; D001920:Bradykinin