Lee J H, Daud A N, Cribbs L L, Lacerda A E, Pereverzev A, Klöckner U, Schneider T, Perez-Reyes E
Department of Physiology, Loyola University Medical Center, Maywood, Illinois 60153, USA.
J Neurosci. 1999 Mar 15;19(6):1912-21. doi: 10.1523/JNEUROSCI.19-06-01912.1999.
Low voltage-activated Ca2+ channels play important roles in pacing neuronal firing and producing network oscillations, such as those that occur during sleep and epilepsy. Here we describe the cloning and expression of the third member of the T-type family, alpha1I or CavT.3, from rat brain. Northern analysis indicated that it is predominantly expressed in brain. Expression of the cloned channel in either Xenopus oocytes or stably transfected human embryonic kidney-293 cells revealed novel gating properties. We compared these electrophysiological properties to those of the cloned T-type channels alpha1G and alpha1H and to the high voltage-activated channels formed by alpha1Ebeta3. The alpha1I channels opened after small depolarizations of the membrane similar to alpha1G and alpha1H but at more depolarized potentials. The kinetics of activation and inactivation were dramatically slower, which allows the channel to act as a Ca2+ injector. In oocytes, the kinetics were even slower, suggesting that components of the expression system modulate its gating properties. Steady-state inactivation occurred at higher potentials than any of the other T channels, endowing the channel with a substantial window current. The alpha1I channel could still be classified as T-type by virtue of its criss-crossing kinetics, its slow deactivation (tail current), and its small (11 pS) conductance in 110 mM Ba2+ solutions. Based on its brain distribution and novel gating properties, we suggest that alpha1I plays important roles in determining the electroresponsiveness of neurons, and hence, may be a novel drug target.
低电压激活的Ca2+通道在调节神经元放电和产生网络振荡（如睡眠和癫痫期间发生的振荡）中起重要作用。在此，我们描述了大鼠脑中T型家族第三个成员alpha1I或CavT.3的克隆和表达。Northern分析表明它主要在脑中表达。在非洲爪蟾卵母细胞或稳定转染的人胚肾-293细胞中克隆通道的表达揭示了新的门控特性。我们将这些电生理特性与克隆的T型通道alpha1G和alpha1H以及由alpha1Ebeta3形成的高电压激活通道的电生理特性进行了比较。alpha1I通道在膜发生小的去极化后开放，类似于alpha1G和alpha1H，但在更正的电位。激活和失活的动力学明显较慢，这使得该通道能够充当Ca2+注入器。在卵母细胞中，动力学甚至更慢，表明表达系统的成分调节其门控特性。稳态失活发生在比任何其他T通道更高的电位，赋予该通道可观的窗电流。由于其交叉动力学、缓慢的失活（尾电流）以及在110 mM Ba2+溶液中的小电导（11 pS），alpha1I通道仍可归类为T型。基于其在脑中的分布和新的门控特性，我们认为alpha1I在决定神经元的电反应性中起重要作用，因此可能是一个新的药物靶点。
