کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2494144 1556657 2010 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mechanisms of inhibition of CaV3.1 T-type calcium current by aliphatic alcohols
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Mechanisms of inhibition of CaV3.1 T-type calcium current by aliphatic alcohols
چکیده انگلیسی

Many aliphatic alcohols modulate activity of various ion channels involved in sensory processing and also exhibit anesthetic capacity in vivo. Although the interaction of one such compound, 1-octanol (octanol) with different T-type calcium channels (T-channels) has been described, the mechanisms of current modulation and its functional significance are not well studied. Using patch-clamp technique, we investigated the mechanisms of inhibition of T-currents by a series of aliphatic alcohols in recombinant human CaV3.1 (α1G) T-channel isoform expressed in human embryonic kidney (HEK) 293 cells and thalamocortical (TC) relay neurons in brain slices of young rats. Octanol, 1-heptanol (heptanol) and 1-hexanol (hexanol) inhibited the recombinant CaV3.1 currents in concentration-dependent manner yielding IC50 values of 362 μM, 1063 μM and 3167 μM, respectively. Octanol similarly inhibited native thalamic CaV3.1 T-currents with an IC50 of 287 μM and diminished burst firing without significant effect on passive membrane properties of these neurons. Inhibitory effect of octanol on T-currents in both native and recombinant cells was accompanied with accelerated macroscopic inactivation kinetics and hyperpolarizing shift in the steady-state inactivation curve. Additionally, octanol induced a depolarizing shift in steady-state activation curves of T-current in TC neurons. Surprisingly, the recovery from fast inactivation at hyperpolarized membrane potentials was accelerated by octanol up 3-fold in native but not recombinant channels. Given the importance of thalamocortical pathways in providing sleep, arousal, and anesthetic states, modulation of thalamic T-currents may at least contribute to the pharmacological effects of aliphatic alcohols.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 59, Issues 1–2, July–August 2010, Pages 58–69
نویسندگان
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