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Activation of Kv7 Potassium Channels Inhibits Intracellular Ca2+ Increases Triggered By TRPV1-Mediated Pain-Inducing Stimuli in F11 Immortalized Sensory Neurons.
Int J Mol Sci. 2019 Sep 04; 20(18)IJ

Abstract

Kv7.2-Kv7.5 channels mediate the M-current (IKM), a K+-selective current regulating neuronal excitability and representing an attractive target for pharmacological therapy against hyperexcitability diseases such as pain. Kv7 channels interact functionally with transient receptor potential vanilloid 1 (TRPV1) channels activated by endogenous and/or exogenous pain-inducing substances, such as bradykinin (BK) or capsaicin (CAP), respectively; however, whether Kv7 channels of specific molecular composition provide a dominant contribution in BK- or CAP-evoked responses is yet unknown. To this aim, Kv7 transcripts expression and function were assessed in F11 immortalized sensorial neurons, a cellular model widely used to assess nociceptive molecular mechanisms. In these cells, the effects of the pan-Kv7 activator retigabine were investigated, as well as the effects of ICA-27243 and (S)-1, two Kv7 activators acting preferentially on Kv7.2/Kv7.3 and Kv7.4/Kv7.5 channels, respectively, on BK- and CAP-induced changes in intracellular Ca2+ concentrations ([Ca2+]i). The results obtained revealed the expression of transcripts of all Kv7 genes, leading to an IKM-like current. Moreover, all tested Kv7 openers inhibited BK- and CAP-induced responses by a similar extent (~60%); at least for BK-induced Ca2+ responses, the potency of retigabine (IC50~1 µM) was higher than that of ICA-27243 (IC50~5 µM) and (S)-1 (IC50~7 µM). Altogether, these results suggest that IKM activation effectively counteracts the cellular processes triggered by TRPV1-mediated pain-inducing stimuli, and highlight a possible critical contribution of Kv7.4 subunits.

Authors+Show Affiliations

Department of Science and Technology, University of Sannio, 82100 Benevento, Italy.Department of Medicine and Health Sciences "V. Tiberio", University of Molise, 86100 Campobasso, Italy.Department of Medicine and Health Sciences "V. Tiberio", University of Molise, 86100 Campobasso, Italy.Department of Medicine and Health Sciences "V. Tiberio", University of Molise, 86100 Campobasso, Italy.Institute of Biomolecular Chemistry, National Research Council, Pozzuoli, 80121 Naples, Italy.Department of Medicine and Health Sciences "V. Tiberio", University of Molise, 86100 Campobasso, Italy.Division of Pharmacology, Department of Neuroscience, University of Naples "Federico II", 80131 Naples, Italy.Department of Science and Technology, University of Sannio, 82100 Benevento, Italy.Department of Science and Technology, University of Sannio, 82100 Benevento, Italy.Division of Pharmacology, Department of Neuroscience, University of Naples "Federico II", 80131 Naples, Italy. mtaglial@unina.it.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31487785

Citation

Ambrosino, Paolo, et al. "Activation of Kv7 Potassium Channels Inhibits Intracellular Ca2+ Increases Triggered By TRPV1-Mediated Pain-Inducing Stimuli in F11 Immortalized Sensory Neurons." International Journal of Molecular Sciences, vol. 20, no. 18, 2019.
Ambrosino P, Soldovieri MV, Di Zazzo E, et al. Activation of Kv7 Potassium Channels Inhibits Intracellular Ca2+ Increases Triggered By TRPV1-Mediated Pain-Inducing Stimuli in F11 Immortalized Sensory Neurons. Int J Mol Sci. 2019;20(18).
Ambrosino, P., Soldovieri, M. V., Di Zazzo, E., Paventi, G., Iannotti, F. A., Mosca, I., Miceli, F., Franco, C., Canzoniero, L. M. T., & Taglialatela, M. (2019). Activation of Kv7 Potassium Channels Inhibits Intracellular Ca2+ Increases Triggered By TRPV1-Mediated Pain-Inducing Stimuli in F11 Immortalized Sensory Neurons. International Journal of Molecular Sciences, 20(18). https://doi.org/10.3390/ijms20184322
Ambrosino P, et al. Activation of Kv7 Potassium Channels Inhibits Intracellular Ca2+ Increases Triggered By TRPV1-Mediated Pain-Inducing Stimuli in F11 Immortalized Sensory Neurons. Int J Mol Sci. 2019 Sep 4;20(18) PubMed PMID: 31487785.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of Kv7 Potassium Channels Inhibits Intracellular Ca2+ Increases Triggered By TRPV1-Mediated Pain-Inducing Stimuli in F11 Immortalized Sensory Neurons. AU - Ambrosino,Paolo, AU - Soldovieri,Maria Virginia, AU - Di Zazzo,Erika, AU - Paventi,Gianluca, AU - Iannotti,Fabio Arturo, AU - Mosca,Ilaria, AU - Miceli,Francesco, AU - Franco,Cristina, AU - Canzoniero,Lorella Maria Teresa, AU - Taglialatela,Maurizio, Y1 - 2019/09/04/ PY - 2019/07/30/received PY - 2019/09/01/revised PY - 2019/09/02/accepted PY - 2019/9/7/entrez PY - 2019/9/7/pubmed PY - 2020/1/15/medline KW - F11 cells KW - XE991 KW - bradykinin KW - capsaicin KW - retigabine JF - International journal of molecular sciences JO - Int J Mol Sci VL - 20 IS - 18 N2 - Kv7.2-Kv7.5 channels mediate the M-current (IKM), a K+-selective current regulating neuronal excitability and representing an attractive target for pharmacological therapy against hyperexcitability diseases such as pain. Kv7 channels interact functionally with transient receptor potential vanilloid 1 (TRPV1) channels activated by endogenous and/or exogenous pain-inducing substances, such as bradykinin (BK) or capsaicin (CAP), respectively; however, whether Kv7 channels of specific molecular composition provide a dominant contribution in BK- or CAP-evoked responses is yet unknown. To this aim, Kv7 transcripts expression and function were assessed in F11 immortalized sensorial neurons, a cellular model widely used to assess nociceptive molecular mechanisms. In these cells, the effects of the pan-Kv7 activator retigabine were investigated, as well as the effects of ICA-27243 and (S)-1, two Kv7 activators acting preferentially on Kv7.2/Kv7.3 and Kv7.4/Kv7.5 channels, respectively, on BK- and CAP-induced changes in intracellular Ca2+ concentrations ([Ca2+]i). The results obtained revealed the expression of transcripts of all Kv7 genes, leading to an IKM-like current. Moreover, all tested Kv7 openers inhibited BK- and CAP-induced responses by a similar extent (~60%); at least for BK-induced Ca2+ responses, the potency of retigabine (IC50~1 µM) was higher than that of ICA-27243 (IC50~5 µM) and (S)-1 (IC50~7 µM). Altogether, these results suggest that IKM activation effectively counteracts the cellular processes triggered by TRPV1-mediated pain-inducing stimuli, and highlight a possible critical contribution of Kv7.4 subunits. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/31487785/Activation_of_Kv7_Potassium_Channels_Inhibits_Intracellular_Ca2+_Increases_Triggered_By_TRPV1_Mediated_Pain_Inducing_Stimuli_in_F11_Immortalized_Sensory_Neurons_ L2 - https://www.mdpi.com/resolver?pii=ijms20184322 DB - PRIME DP - Unbound Medicine ER -