BRADYKININ-INDUCED MODULATION OF CALCIUM SIGNALS IN RAT DORSAL-ROOT GANGLION NEURONS INVITRO

We used combined patch-clamp-microfluorimetric recordings to examine the effects of bradykinin on [Ca2+]i transients and the Ca2+ current (I(Ca)) in rat dorsal root ganglion neurons in vitro. Bradykinin increased [Ca2+]i in approximately 20% of dorsal root ganglion cells examined and inhibited the I(Ca) in approximately 65% of dorsal root ganglion cells. Bradykinin also inhibited the I(Ca) when [Ca2+]i was buffered with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid or when Ba2+ was the charge carrier. When I(Ca)'s of increasing duration were elicited in these neurons, [Ca2+]i transients were produced that increased in amplitude but eventually approached an asymptote at longer voltage steps. Similarly, the amplitude of the [Ca2+]i transient also approached an asymptote in current-clamp recordings when cells were induced to fire a large number of action potentials. The bradykinin-induced inhibition of the amplitude of the [Ca2+]i transient was more pronounced at shorter voltage steps. At pulse durations that produced asymptotic [Ca2+]i signals, bradykinin no longer decreased the amplitude of the rise in [Ca2+]i, although it still reduced the I(Ca). In current-clamp recordings, bradykinin also reduced the [Ca2+]i signal that accompanied the generation of action potentials, but again bradykinin was more effective for shorter spike trains. Bradykinin also depolarized the majority of neurons (65%). The reduction in [Ca2+]i produced by bradykinin in sensory neurons may be an important factor contributing to bradykinin-induced excitation of primary sensory afferents.