Sodium and calcium current-mediated pacemaker neurons and respiratory rhythm generation
Sodium and calcium current-mediated pacemaker neurons and respiratory rhythm generation
复制标题
DOI：
10.1523/jneurosci.2237-04.2005
复制
发表时间：
2005-01-12
影响因子：
5.3
通讯作者：
Feldman, JL
中科院分区：
文献类型：
--
作者：
Del Negro, CA;Morgado-Valle, C;Feldman, JL
哺乳动物的呼吸运动模式起源于脑干网络。起搏神经元是否扮演着必须的角色仍然是一个关键的悬而未决的问题。我们在新生啮齿动物的切片标本中进行了前Botzinger复合体的全细胞记录，并测试了起搏器的活动。我们观察到持续钠电流(I-NAP)在出生后0(P0)-P5和P8-P10脑片中类似于5%的吸气神经元的爆发。I-NAP介导的爆发是电压依赖性的，并可被20微米利鲁唑(RIL)阻断。我们发现，在P8-P10脑片中，7.5%的吸气神经元有钙电流(I-Ca)依赖性爆发，但在P0-P5脑片中，这种细胞非常罕见(0.6%)。这种爆发不依赖于电压，并可被100um的Cd~(2+)或氟苯那酸(FFA)(10~200um)所阻断，这表明钙激活的内向阳离子电流(I-CAN)是爆发发生的基础。这些数据证实了我们的观察结果，即暴露于RIL的P0-P5脑片中几乎没有起搏神经元(如果有的话)，但仍保持呼吸节律。我们还发现，20微米的TTX或联合应用20微米的RIL+FFA(100-200微米)会停止呼吸节律，但加入2微米的P物质则重新启动呼吸节律。我们得出结论，I-NAP和I-可以增强神经元的兴奋性和促进节律的产生，即使它们的大小不足以支持单个神经元的爆发性起搏器活动。当I-NAP和I-Can被药物去除时，可以通过增强神经兴奋性来维持节律，这与起搏器的基本机制不一致，即通过前Botzinger复合体导致呼吸节律发生。
The breathing motor pattern in mammals originates in brainstem networks. Whether pacemaker neurons play an obligatory role remains a key unanswered question. We performed whole-cell recordings in the preBotzinger Complex in slice preparations from neonatal rodents and tested for pacemaker activity. We observed persistent Na+ current (I-NaP)-mediated bursting in similar to5% of inspiratory neurons in postnatal day 0 (P0)-P5 and in P8-P10 slices. I-NaP-mediated bursting was voltage dependent and blocked by 20 muM riluzole (RIL). We found Ca2+ current (I-Ca)-dependent bursting in 7.5% of inspiratory neurons in P8-P10 slices, but in P0-P5 slices these cells were exceedingly rare (0.6%). This bursting was voltage independent and blocked by 100 muM Cd2+ or flufenamic acid (FFA) (10-200 muM), which suggests that a Ca2+-activated inward cationic current (I-CAN) underlies burst generation. These data substantiate our observation that P0-P5 slices exposed to RIL contain few (if any) pacemaker neurons, yet maintain respiratory rhythm. We also show that 20 nM TTX or coapplication of 20 muM RIL + FFA (100-200 muM) stops the respiratory rhythm, but that adding 2 muM substance P restarts it. We conclude that I-NaP and I-CAN enhance neuronal excitability and promote rhythmogenesis, even if their magnitude is insufficient to support bursting-pacemaker activity in individual neurons. When I-NaP and I-CAN are removed pharmacologically, the rhythm can be maintained by boosting neural excitability, which is inconsistent with a pacemaker-essential mechanism of respiratory rhythmogenesis by the preBotzinger complex.