title: Bradykinin decreases K(+) and increases Cl(-) conductances in vagal afferent neurones of the guinea pig.
abstract: Bradykinin (BK) is an inflammatory mediator that can excite and sensitize primary afferent neurones. The nature of the ionic channels underlying the excitatory actions of BK is still incompletely understood. Using whole-cell patch-clamp recording from acutely dissociated nodose ganglion neurones (NGNs) we have examined the ionic mechanism responsible for BK's excitatory effect. Bath-applied BK (0.1 microM) depolarized the membrane potential (29 +/- 3.1 mV, n= 7), evoked action potentials, and induced an inward ionic current (I(BK)) with two distinctive membrane conductances (g(m)). Initially, g(m) decreased; the ionic current associated with this g(m) had a reversal potential (E(rev)) value of -87 +/- 1.1 mV (n= 26), a value close to E(K) (-89 mV). Subsequently, g(m) increased; the ionic current associated with this g(m) had an estimated E(rev) of 49 +/- 4.3 mV (n= 23). When the second component was isolated from the first component, by replacing [K(+)](o) with Cs(+), E(rev) was 20 +/- 4.7 mV (n= 10). Replacing external NaCl with NMDG-Cl or choline-Cl, or reducing [Ca(2+)](o) did not significantly diminish I(BK). After replacing external NaCl with sodium isethionate, E(rev) for the second component shifted to 56 +/- 8.8 mV (n= 4), a value close to the E(Cl) (66 mV). The second component was inhibited by intracellular BAPTA or by bath application of niflumic acid (100 microM), a Ca(2+)-activated Cl(-) channel blocker. These results suggest that the first and second components of I(BK) are produced by a decrease in K(+) conductance and an increase in Ca(2+)-activated Cl(-) conductance, respectively. The BK-evoked Cl(-) conductance in NGNs may be the first demonstration of an inflammatory mediator exciting primary afferents via an anion channel.
authors.affiliation: University of Maryland School of Medicine, Department of Pharmacology and Experimental Therapeutics, Room 4-002, Bressler Research Building, 655 West Baltimore Street, Baltimore, MD 21201-1559, USA.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Oh
authors.forename: Daniel
authors.initials: D
authors.lastname: Weinreich
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018118:Chloride Channels / Q000502:physiology; D002712:Chlorides / Q000378:metabolism*; D006168:Guinea Pigs; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D014132:Trachea / Q000294:innervation
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D011188:Potassium; D001920:Bradykinin; D002118:Calcium