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Department of Pharmacology and Experimental Therapeutics, University of Maryland, School of Medicine, Baltimore, MD, USA

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 µM) 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 [Ca²⁺]_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 µM), 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.

(Received 11 April 2004; accepted after revision 24 May 2004; first published online 28 May 2004)
Corresponding author D. Weinreich: 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. Email: dweinrei{at}umaryland.edu

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