Expression of three distinct families of calcium-activated chloride channel genes in the mouse dorsal root ganglion

Objective A calcium-activated chloride current （ICl（Ca）） has been observed in medium-sized sensory neurons of the dorsal root ganglion （DRG）. Axotomy of the sciatic nerve induces a similar current in the majority of medium and large diameter neurons. Our aim is to identify the molecule（s） underlying this current. Methods Using conventional and quantitative RT-PCR, we examined the expression in DRG of members of three families of genes, which have been shown to have latch） current inducing properties. Results We showed the detection of transcripts representing several members of these families, i.e. chloride channel calciumactivated （CLCA）, Bestrophin and Tweety gene families in adult DRG, in the normal state and 3 d after sciatic nerve section, a model for peripheral nerve injury. Conclusion Our analysis revealed that that mBestl and Tweety2 appear as the best candidates to play a role in the injury-induced Icl（Ca） in DRG neurons.

Pharmacological evaluation of smooth muscle relaxant and cardiac-modulation potential of Phyla nodiflora in ex-vivo and in-vivo experiments

Objective: To investigate the pharmacological basis of its uses of Phyla nodiflora(P. nodiflora) for the treatment of anomalies predominantly by smooth muscle containing tissues such as gastrointestinal/vascular/broncho spasm and cardiovascular modulation.Methods: The crude hydroalcoholic extract of P. nodiflora(Pn.Cr) and its fractions were evaluated on isolated rabbit jejunum, rat trachea, aorta and atrium. To access the contractile or relaxant effects of testing materials, the tissues were mounted in isolated organ bath and responses were recorded with transducers coupled with data acquisition system.BALB/c mice were challenged with castor oil for the assessment of in-vivo antidiarrheal activity. Normotensive rats were used for in-vivo hypotensive study.Results: Hydroalcoholic extract of Pn.Cr at variable concentrations inhibited the natural spontaneous rhythm and 80 mmol/L K^+ mediated contractions in isolated segment of jejunum with EC_(50) values of 3.18 and 1.91 mg/mL respectively. Verapamil, a Ca^(2+) channel blocker, demonstrated akin pattern in jejunum and therefore possibly suggesting calcium blocking activity. On isolated rat tracheal tissue, Pn.Cr showed relaxation of high-K^+and carbachol mediated contractions(EC_(50) values: 1.24 and 2.42 mg/mL). Pn.Cr treatment relaxed the rat aortic ring in a cumulative doses with high-K^+ and phenylephrine-induced contractions(EC_(50) values 0.25 and 0.92 mg/mL). Activity based fractionation of Pn.Cr showed that dichloromethane fraction was more potent for relaxing the tissues spasm compared to aqueous fraction. In-vivo experiments, significant protection by Pn.Cr(P < 0.05) was observed in castor oil-induced diarrhea(50–500 mg/kg)whereas hypotensive effect in anesthetized rats was seen at the dose range of 1–10 mg/kg of Pn.Cr(P < 0.05).Conclusion: This study suggests the blockage of calcium channel in the smooth muscles as a pharmacological application to make usage of P. nodiflora in the management of diarrhea, asthma and hypotensive effect.

Highlights for the 6th International Ion Channel Conference:ion channel structure,function,disease and therapeutics

To foster communication and interactions amongst international scholars and scientists in the field of ion channel research, the 6 th International Ion Channel Conference(IICC-2017) was held between June 23–27, 2017 in the eastern coastal city of Qingdao, China. The meeting consisted of 450 attendees and 130 speakers and poster presenters. The program consisted of research progress, new findings and ongoing studies that were focused on(1) Ion channel structure and function;(2) Ion channel physiology and human diseases;(3) Ion channels as targets for drug discovery;(4) Technological advances in ion channel research. An insightful overview was presented on the structure and function of the mechanotransduction channel Drosophila NOMPC(No mechanoreceptor potential C), a member of the transient receptor potential(TRP) channel family. Recent studies on Transmembrane protein 16 or Anoctamin-1(TMEM16A, a member of the calcium-activated chloride channel [CaCC] family) were summarized as well. In addition, topics for ion channel regulation, homeostatic feedback and brain disorders were thoroughly discussed. The presentations at the IICC-2017 offer new insights into our understanding of ion channel structures and functions, and ion channels as targets for drug discovery.