کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5738551 1615060 2017 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research articleMechanism of inhibition by chlorpromazine of the human pain threshold sodium channel, Nav1.7
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Research articleMechanism of inhibition by chlorpromazine of the human pain threshold sodium channel, Nav1.7
چکیده انگلیسی


- CPZ blocks the hNav1.7 channel, independent of calmodulin.
- CPZ stabilizes inactivation states and decreases the availability of hNav1.7.
- CPZ blocks the hNav1.7 current in concentration-, state- and use-dependent manners.

Chlorpromazine is a phenothiazine derivative which is primarily used for schizophrenia and occasionally for migraine. Because Nav1.7 plays an important role in pain sensation, we investigated whether chlorpromazine blocks the human Nav1.7 (hNav1.7) sodium current in HEK293 cells stably expressing hNav1.7 using the whole-cell patch-clamp technique. The peak current of hNav1.7 was reduced by chlorpromazine in a concentration-dependent manner with a half-maximal inhibitory concentration of 25.9 ± 0.6 μM and a Hill coefficient of 2.3 ± 0.1. The calmodulin inhibitory peptide did not abolish the blockade of hNav1.7 currents by chlorpromazine. The blockade of hNav1.7 currents by chlorpromazine was completely and repeatedly reversible after washout. The half-maximal voltage of activation of hNav1.7 was not changed by chlorpromazine. However, chlorpromazine caused hyperpolarized the steady-state inactivation of hNav1.7. The recovery from inactivation in the presence of chlorpromazine was slower than in the absence of chlorpromazine. Chlorpromazine also showed strong use-dependent inhibition of the hNav1.7 current. Our results demonstrate that chlorpromazine blocks the hNav1.7 current in concentration-, state- and use-dependent manners and suggest that it merits further study for potential use in pain management.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 639, 3 February 2017, Pages 1-7
نویسندگان
, , , , ,