Rocher Asunción, Geijo-Barrientos Emilio, Cáceres Ana Isabel, Rigual Ricardo, González Constancio, Almaraz Laura
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Campus de San Juan, 03550 San Juan, Alicante, Spain.
J Physiol. 2005 Jan 15;562(Pt 2):407-20. doi: 10.1113/jphysiol.2004.075523. Epub 2004 Nov 4.
We have defined Ca2+ channel subtypes expressed in rabbit carotid body (CB) chemoreceptor cells and their participation in the stimulus-evoked catecholamine (CA) release. Ca2+ currents (I(Ca)) activated at -30 mV, peaked at +10 mV and were fully blocked by 200 microm Cd2+. L-type channels (sensitive to 2 microm nisoldipine) activated at -30 mV and carried 21 +/- 2% of total I(Ca). Non-L-type channels activated at potentials positive to -10 mV and carried: N channels (sensitive to 1 microM omega-conotoxin-GVIA) 16 +/- 1% of total I(Ca), P/Q channels (sensitive to 3 microM omega-conotoxin-MVIIC after nisoldipine plus GVIA) 23 +/- 3% of total I(Ca) and R channels (resistant to all blockers combined) 40 +/- 3% of total I(Ca). CA release induced by hypoxia, hypercapnic acidosis, dinitrophenol (DNP) and high K(+)(o) in the intact CB was inhibited by 79-98% by 200 microm Cd2+. Hypoxia, hypercapnic acidosis and DNP, depolarized chemoreceptor cells and eventually generated repetitive action potential discharge. Nisoldipine plus MVIIC nearly abolished the release of CAs induced by hypoxia and hypercapnic acidosis and reduced by 74% that induced by DNP. All these secretory responses were insensitive to GVIA. 30 and 100 mm K(+)(o) brought resting membrane potential (E(m)) of chemoreceptor cells (-48.1 +/- 1.2 mV) to -22.5 and +7.2 mV, respectively. Thirty millimolar K(+)(o)-evoked release was abolished by nisoldipine but that induced by 100 mm K(+)(o) was mediated by activation of L, N, and P/Q channels. Data show that tested stimuli depolarize rabbit CB chemoreceptor cells and elicit CA release through Ca2+ entry via voltage-activated channels. Only L and P/Q channels are tightly coupled to the secretion of CA.
我们已经明确了兔颈动脉体（CB）化学感受细胞中表达的Ca2+通道亚型及其在刺激诱发的儿茶酚胺（CA）释放中的作用。Ca2+电流（I(Ca)）在-30 mV时激活，在+10 mV时达到峰值，并被200 μM Cd2+完全阻断。L型通道（对2 μM尼索地平敏感）在-30 mV时激活，占总I(Ca)的21±2%。非L型通道在高于-10 mV的电位时激活，其中：N通道（对1 μMω-芋螺毒素-GVIA敏感）占总I(Ca)的16±1%，P/Q通道（在尼索地平加GVIA后对3 μMω-芋螺毒素-MVIIC敏感）占总I(Ca)的23±3%，R通道（对所有联合阻断剂均有抗性）占总I(Ca)的40±3%。在完整的CB中，缺氧、高碳酸血症性酸中毒、二硝基苯酚（DNP）和高K+(o)诱导的CA释放被200 μM Cd2+抑制了79 - 98%。缺氧、高碳酸血症性酸中毒和DNP使化学感受细胞去极化，并最终产生重复的动作电位发放。尼索地平加MVIIC几乎完全消除了缺氧和高碳酸血症性酸中毒诱导的CA释放，并使DNP诱导的释放减少了74%。所有这些分泌反应对GVIA均不敏感。30和100 mM K+(o)分别使化学感受细胞的静息膜电位（E(m)）（-48.1±1.2 mV）变为-22.5和+7.2 mV。30 mM K+(o)诱发的释放被尼索地平消除，但100 mM K+(o)诱发的释放是由L、N和P/Q通道的激活介导的。数据表明，所测试的刺激使兔CB化学感受细胞去极化，并通过电压激活通道的Ca2+内流引发CA释放。只有L和P/Q通道与CA的分泌紧密偶联。
