Rothman Jason S, Manis Paul B
The Center for Hearing Science, Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
J Neurophysiol. 2003 Jun;89(6):3083-96. doi: 10.1152/jn.00126.2002.
Neurons in the ventral cochlear nucleus (VCN) express three distinct K+ currents that differ in their voltage and time dependence, and in their inactivation behavior. In the present study, we quantitatively analyze the voltage-dependent kinetics of these three currents to gain further insight into how they regulate the discharge patterns of VCN neurons and to provide supporting data for the identification of their channel components. We find the transient A-type K+ current (IA) exhibits fourth-order activation kinetics (a4), and inactivates with one or two time constants. A second inactivation rate (leading to an a4bc kinetic description) is required to explain its recovery from inactivation. The dendrotoxin-sensitive low-threshold K+ current (ILT) also activates with fourth-order kinetics (w4) but shows slower, incomplete inactivation. The high-threshold K+ current (IHT) appears to consist of two kinetically distinct components (n2 + p). The first component activates approximately 10 mV positive to the second and has second-order kinetics. The second component activates with first-order kinetics. These two components also contribute to two kinetically distinct currents upon deactivation. The kinetic behavior of IHT was indistinguishable amongst cell types, suggesting the current is mediated by the same K+ channels amongst VCN neurons. Together these results provide a basis for more realistic modeling of VCN neurons, and provide clues regarding the molecular basis of the three K+ currents.
腹侧耳蜗核(VCN)中的神经元表达三种不同的钾离子电流,它们在电压和时间依赖性以及失活行为方面存在差异。在本研究中,我们定量分析了这三种电流的电压依赖性动力学,以进一步了解它们如何调节VCN神经元的放电模式,并为识别其通道成分提供支持数据。我们发现瞬时A型钾离子电流(IA)表现出四阶激活动力学(a4),并以一个或两个时间常数失活。需要第二个失活速率(导致a4bc动力学描述)来解释其从失活状态的恢复。树突毒素敏感的低阈值钾离子电流(ILT)也以四阶动力学(w4)激活,但显示出较慢的、不完全的失活。高阈值钾离子电流(IHT)似乎由两个动力学上不同的成分组成(n2 + p)。第一个成分比第二个成分在正10 mV左右激活,具有二阶动力学。第二个成分以一阶动力学激活。这两个成分在去激活时也对两个动力学上不同的电流有贡献。IHT的动力学行为在不同细胞类型之间没有区别,这表明该电流在VCN神经元中由相同的钾离子通道介导。这些结果共同为VCN神经元更真实的建模提供了基础,并为三种钾离子电流的分子基础提供了线索。