Persistent sodium current, membrane properties and bursting behavior of pre-Botzinger complex inspiratory neurons in vitro
Persistent sodium current, membrane properties and bursting behavior of pre-Botzinger complex inspiratory neurons in vitro
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DOI：
10.1152/jn.00081.2002
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发表时间：
2002-11-01
影响因子：
2.5
通讯作者：
Smith, JC
中科院分区：
文献类型：
--
作者：
Del Negro, CA;Koshiya, N;Smith, JC
在体外节律性呼吸网络活跃的脑干切片制备中，我们测量了新生大鼠pre-Botzinger复合体（pre-BotC）的起搏器和非破裂吸气神经元的持续Na（+）电流和膜特性。在全细胞记录中，当隔离电压敏感成分时，缓慢的电压斜坡（小于或等于100 mV/s）使快速的、产生尖峰的Na（+）电流失活，并产生n形的电流-电压关系，其非单调的负斜率区域在-60到-35 mV之间。底层电流是TTX敏感的持久Na（+）电流（I(NaP)），因为内向电流以缓慢的电压斜坡速度（3.3-100 mV/s）存在，并且电流被1 muM TTX阻断。我们在Cd（2+）和某些情况下的四乙基铵（TEA）存在下，在减去电压不敏感的“泄漏”电流（I(leak)）后，测量了I（NaP）的生物物理特性。在-30 mV的膜电位下，峰I（NaP）变化范围为-50 ~ -200 pA。降低电压坡道的速度会导致时间依赖性I（NaP）失活，但该电流在坡道速度低至3.3 mV/s时存在。I（NaP）在-60 mV激活，在-40 mV附近获得半最大值激活。I（NaP）的阈下电压依赖性和缓慢失活动力学，与I（NaP）的数学模型中爆发生成机制非常相似，表明I（NaP）在体外主要影响botc前吸入起搏器神经元的爆发动力学。我们还发现，持续Na（+）电导与漏电导的比值(g（NaP)/g(leak)）可以区分爆裂性起搏器和非爆裂性呼吸神经元的表型亚群：非起搏器细胞的起搏器神经元表现为g(NaP)/g(leak) > g(NaP)/g(leak) （P < 0.0002）。我们得出结论，I（NaP）在botc前的吸气神经元中普遍表达，并且在异质吸气神经元群体中爆发起搏器行为是由这两种电导g（NaP）和g（Leak）的特定比例实现的。
We measured persistent Na(+) current and membrane properties of bursting-pacemaker and nonbursting inspiratory neurons of the neonatal rat pre-Botzinger complex (pre-BotC) in brain stem slice preparations with a rhythmically active respiratory network in vitro. In whole-cell recordings, slow voltage ramps (less than or equal to100 mV/s) inactivated the fast, spike-generating Na(+) current and yielded N-shaped current-voltage relationships with nonmonotonic, negative-slope regions between -60 and -35 mV when the voltage-sensitive component was isolated. The underlying current was a TTX-sensitive persistent Na(+) current (I(NaP)) since the inward current was present at slow voltage ramp speeds (3.3-100 mV/s) and the current was blocked by 1 muM TTX. We measured the biophysical properties of I(NaP) after subtracting the voltage-insensitive "leak" current (I(Leak)) in the presence of Cd(2+) and in some cases tetraethylammonium (TEA). Peak I(NaP) ranged from -50 to -200 pA at a membrane potential of -30 mV. Decreasing the speed of the voltage ramp caused time-dependent I(NaP) inactivation, but this current was present at ramp speeds as low as 3.3 mV/s. I(NaP) activated at -60 mV and obtained half-maximal activation near -40 mV. The subthreshold voltage dependence and slow inactivation kinetics of I(NaP), which closely resemble those of I(NaP) mathematically modeled as a burst-generation mechanism in pacemaker neurons of the pre-BotC, suggest that I(NaP) predominantly influences bursting dynamics of pre-BotC inspiratory pacemaker neurons in vitro. We also found that the ratio of persistent Na(+) conductance to leak conductance (g(NaP)/g(Leak)) can distinguish the phenotypic subpopulations of bursting pacemaker and nonbursting inspiratory neurons: pacemaker neurons showed g(NaP) /g(Leak) > g(NaP) / g(Leak) in nonpacemaker cells (P < 0.0002). We conclude that I(NaP) is ubiquitously expressed by pre-BotC inspiratory neurons and that bursting pacemaker behavior within the heterogeneous population of inspiratory neurons is achieved with specific ratios of these two conductances, g(NaP) and g(Leak).