Transient receptor potential melastatin 3 (TRPM3) channels contribute to nodose afferent and brainstem nucleus tractus solitarii (nTS) activity. Exposure to short, sustained hypoxia (SH) and chronic intermittent hypoxia (CIH) enhances nTS activity, although the mechanisms are unknown. We hypothesized TRPM3 may contribute to increased neuronal activity in nTS-projecting nodose ganglia viscerosensory neurons, and its influence is elevated following hypoxia. Rats were exposed to either room air (normoxia), 24-h of 10 % O₂ (SH), or CIH (episodic 6 % O₂ for 10d). A subset of neurons from normoxic rats were exposed to in vitro incubation for 24-h in 21 % or 1 % O₂. Intracellular Ca²⁺ of dissociated neurons was monitored via Fura-2 imaging. Ca²⁺ levels increased upon TRPM3 activation via Pregnenolone sulfate (Preg) or CIM0216. Preg responses were eliminated by the TRPM3 antagonist ononetin, confirming agonist specificity. Removal of extracellular Ca²⁺ also eliminated Preg response, further suggesting Ca²⁺ influx via membrane-bound channels. In neurons isolated from SH-exposed rats, the TRPM3 elevation of Ca²⁺ was greater than in normoxic-exposed rats. The SH increase was reversed following a subsequent normoxic exposure. RNAScope demonstrated TRPM3 mRNA was greater after SH than in Norm ganglia. Incubating dissociated cultures from normoxic rats in 1 % O₂ (24-h) did not alter the Preg Ca²⁺ responses compared to their normoxic controls. In contrast to in vivo SH, 10d CIH did not alter TRPM3 elevation of Ca²⁺. Altogether, these results demonstrate a hypoxia-specific increase in TRPM3-mediated calcium influx.

瞬时受体电位melastatin 3 (TRPM3) 通道有助于结状传入和脑干孤束核 (nTS) 活性。短暂持续缺氧(SH) 和慢性间歇性缺氧 (CIH) 会增强 nTS 活性，但其机制尚不清楚。我们假设 TRPM3 可能有助于增加nTS 投射结状神经节内脏感觉神经元的神经元活动，并且其影响在缺氧后增强。大鼠暴露于室内空气（含氧量正常）、24 小时 10% O ₂ (SH) 或 CIH（间歇性 6% O ₂，持续 10 天）。将常氧大鼠的一部分神经元暴露于 21% 或 1% O ₂的体外培养 24 小时。细胞内Ca ²⁺通过 Fura-2 成像监测游离神经元的数量。通过硫酸孕烯醇酮 (Preg) 或 CIM0216 激活 TRPM3 后， Ca ^{2+水平增加。}TRPM3 拮抗剂 ononetin 消除了 Preg 反应，证实了激动剂的特异性。^{细胞外 Ca 2+}的去除也消除了 Preg 反应，进一步表明 Ca ²⁺通过膜结合通道流入。^{在从SH暴露的大鼠中分离的神经元中，Ca 2+}的TRPM3升高高于常氧暴露的大鼠。在随后的常氧暴露后，SH 的增加被逆转。RNAScope 证明 SH 后 TRPM3 mRNA 高于正常神经节。在 1% O _{2中孵育常氧大鼠的分离培养物}与含氧量正常的对照相比，(24-h) 并没有改变 Preg Ca ^2+反应。与体内 SH 相比，10d CIH 不会改变 TRPM3 的 Ca ^2+升高。总而言之，这些结果表明 TRPM3 介导的钙流入存在缺氧特异性增加。