Wilson Jennifer M M, Coderre Elaine, Renaud Leo P, Spanswick David
Neurosciences, Ottawa Health Research Institute, University of Ottawa, Ontario, Canada K1Y 4E9, UK.
J Physiol. 2002 Dec 15;545(3):945-60. doi: 10.1113/jphysiol.2002.023390.
The intravascular release of adrenal catecholamines is a fundamental homeostatic process mediated via thoracolumbar spinal sympathetic preganglionic neurones (AD-SPN). To understand mechanisms regulating their excitability, whole-cell patch-clamp recordings were obtained from 54 retrogradely labelled neonatal rat AD-SPN. Passive membrane properties included a mean resting membrane potential, input resistance and time constant of -62 +/- 6 mV, 410 +/- 241 MOmega and 104 +/- 53 ms, respectively. AD-SPN were homogeneous with respect to their active membrane properties. These active conductances included transient outward rectification, observed as a delayed return to rest at the offset of the membrane response to hyperpolarising current pulses, with two components: a fast 4-AP-sensitive component (A-type conductance), contributing to the after-hyperpolarisation (AHP) and spike repolarisation; a slower prolonged Ba(2+)-sensitive component (D-like conductance). All AD-SPN expressed a Ba(2+)-sensitive instantaneous inwardly rectifying conductance activated at membrane potentials more negative than around -80 mV. A potassium-mediated, voltage-dependent sustained outward rectification activated at membrane potentials between -35 and -15 mV featured an atypical pharmacology with a component blocked by quinine, reduced by low extracellular pH and arachidonic acid, but lacking sensitivity to Ba(2+), TEA and intracellular Cs(+). This quinine-sensitive outward rectification contributes to spike repolarisation. Following block of potassium conductances by Cs(+) loading, AD-SPN revealed the capability for autorhythmicity and burst firing, mediated by a T-type Ca(2+) conductance. These data suggest the output capability is dynamic and diverse, and that the range of intrinsic membrane conductances expressed endow AD-SPN with the ability to generate differential and complex patterns of activity. The diversity of intrinsic membrane properties expressed by AD-SPN may be key determinants of neurotransmitter release from SPN innervating the adrenal medulla. However, factors other than active membrane conductances of AD-SPN must ultimately regulate the differential ratio of noradrenaline (NA) versus adrenaline (A) release secreted in response to various physiological and environmental demands.
肾上腺儿茶酚胺的血管内释放是一个通过胸腰段脊髓交感神经节前神经元(AD-SPN)介导的基本稳态过程。为了解调节其兴奋性的机制,我们从54只逆行标记的新生大鼠AD-SPN中获得了全细胞膜片钳记录。被动膜特性包括平均静息膜电位、输入电阻和时间常数,分别为-62±6 mV、410±241 MΩ和104±53 ms。AD-SPN在其主动膜特性方面是同质的。这些主动电导包括瞬时外向整流,表现为在对超极化电流脉冲的膜反应结束时延迟恢复到静息状态,有两个成分:一个快速的4-AP敏感成分(A型电导),有助于超极化后电位(AHP)和动作电位复极化;一个较慢的延长的Ba(2+)敏感成分(D样电导)。所有AD-SPN都表达了一种Ba(2+)敏感的瞬时内向整流电导,在膜电位比约-80 mV更负时被激活。一种钾介导的、电压依赖性的持续外向整流在膜电位-35至-15 mV之间被激活,其药理学特性不典型,有一个成分被奎宁阻断,在低细胞外pH和花生四烯酸作用下降低,但对Ba(2+)、TEA和细胞内Cs(+)不敏感。这种奎宁敏感的外向整流有助于动作电位复极化。在用Cs(+)负载阻断钾电导后,AD-SPN显示出自律性和爆发性放电的能力,由T型Ca(2+)电导介导。这些数据表明输出能力是动态多样的,并且所表达的内在膜电导范围赋予AD-SPN产生不同和复杂活动模式的能力。AD-SPN所表达的内在膜特性的多样性可能是支配肾上腺髓质的SPN释放神经递质的关键决定因素。然而,除了AD-SPN的主动膜电导之外,其他因素最终必须调节响应各种生理和环境需求而分泌的去甲肾上腺素(NA)与肾上腺素(A)释放的差异比例。