Bradykinin decreases K+ and increases Cl- conductances in vagal afferent neurones of the guinea pig

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 mum) 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 decreased; the ionic current associated with this gm had a reversal potential (E-rev) value of -87 +/- 11.1 mV (n = 26), a value close to E-K (-89 MV)Subsequently, g(m) increased; the ionic current associated with this gm 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 [Ca2+](o) did not significantly diminish I-BK. After replacing external NaCl with sodium isethionate, Erev 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 mum), a Ca2+-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 Ca2+-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.