Trigeminal Ganglion Neurons of Mice Show Intracellular Chloride Accumulation and Chloride-Dependent Amplification of Capsaicin-Induced Responses

نویسندگان

  • Nicole Schöbel
  • Debbie Radtke
  • Matthias Lübbert
  • Günter Gisselmann
  • Ramona Lehmann
  • Annika Cichy
  • Benjamin S. P. Schreiner
  • Janine Altmüller
  • Alan C. Spector
  • Jennifer Spehr
  • Hanns Hatt
  • Christian H. Wetzel
چکیده

Intracellular Cl(-) concentrations ([Cl(-)](i)) of sensory neurons regulate signal transmission and signal amplification. In dorsal root ganglion (DRG) and olfactory sensory neurons (OSNs), Cl(-) is accumulated by the Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1), resulting in a [Cl(-)](i) above electrochemical equilibrium and a depolarizing Cl(-) efflux upon Cl(-) channel opening. Here, we investigate the [Cl(-)](i) and function of Cl(-) in primary sensory neurons of trigeminal ganglia (TG) of wild type (WT) and NKCC1(-/-) mice using pharmacological and imaging approaches, patch-clamping, as well as behavioral testing. The [Cl(-)](i) of WT TG neurons indicated active NKCC1-dependent Cl(-) accumulation. Gamma-aminobutyric acid (GABA)(A) receptor activation induced a reduction of [Cl(-)](i) as well as Ca(2+) transients in a corresponding fraction of TG neurons. Ca(2+) transients were sensitive to inhibition of NKCC1 and voltage-gated Ca(2+) channels (VGCCs). Ca(2+) responses induced by capsaicin, a prototypical stimulus of transient receptor potential vanilloid subfamily member-1 (TRPV1) were diminished in NKCC1(-/-) TG neurons, but elevated under conditions of a lowered [Cl(-)](o) suggesting a Cl(-)-dependent amplification of capsaicin-induced responses. Using next generation sequencing (NGS), we found expression of different Ca(2+)-activated Cl(-) channels (CaCCs) in TGs of mice. Pharmacological inhibition of CaCCs reduced the amplitude of capsaicin-induced responses of TG neurons in Ca(2+) imaging and electrophysiological recordings. In a behavioral paradigm, NKCC1(-/-) mice showed less avoidance of the aversive stimulus capsaicin. In summary, our results strongly argue for a Ca(2+)-activated Cl(-)-dependent signal amplification mechanism in TG neurons that requires intracellular Cl(-) accumulation by NKCC1 and the activation of CaCCs.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Calcium responses of chicken trigeminal ganglion neurons to methyl anthranilate and capsaicin.

Using digital fluorescence imaging, we determined the effects of methyl anthranilate (MA), an avian irritant, and capsaicin (CAP), a mammalian irritant, on intracellular calcium ([Ca(2+)](i)) in chicken trigeminal neurons. Concentration-response functions indicated that the threshold for inducing increases in [Ca(2+)](i) was higher for CAP (30 micromol l(-1)) than for MA (10 micromol l(-1)). Th...

متن کامل

The responses of rat trigeminal ganglion neurons to capsaicin and two nonpungent vanilloid receptor agonists, olvanil and glyceryl nonamide.

Capsaicin, the pungent ingredient in hot pepper, activates and subsequently desensitizes a subset of polymodal nociceptors. Because its initial application to skin produces pain, nonpungent analogs such as olvanil and glyceryl nonivamide (GLNVA) were synthesized to enhance its clinical use. To explore how these nonpungent analogs differ from capsaicin, whole-cell patch-clamp recordings were per...

متن کامل

Changes in osmolality sensitize the response to capsaicin in trigeminal sensory neurons.

Changes in tonicity in the peripheral nervous system can activate nociceptors and produce pain. Under local inflammatory conditions the peripheral terminals of nociceptors are subject to deviations from isotonicity. Previously it was shown that several members of the TRP(V) family of ion channels are responsive to changes in tonicity. Here we explore how changes in tonicity affect TRPV1 recepto...

متن کامل

Chloride channel protein 2 prevents glutamate-induced apoptosis in retinal ganglion cells

Objective(s): The purpose of this study was to investigate the role of chloride channel protein 2 (ClC-2) in glutamate-induced apoptosis in the retinal ganglion cell line (RGC-5). Materials and Methods: RGC-5 cells were treated with 1 mM glutamate for 24 hr. The expression of ClC-2, Bax, and Bcl-2 was detected by western blot analysis. Cell survival and apoptosis were measured by 3-(4,5-dimeth...

متن کامل

Modulation of IA currents by capsaicin in rat trigeminal ganglion neurons.

When capsaicin, the pungent compound in hot pepper, is applied to epithelia it produces pain, allodynia, and hyperalgesia. We investigated, using whole cell path clamp, whether some of these responses induced by capsaicin could be a consequence of capsaicin blocking I(A) currents, a reduction in which, such as occurs in injury, increases neuronal excitability. In capsaicin-sensitive (CS) rat tr...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2012