Rammelkamp Center for Education and Research, MetroHealth Medical Center Campus, Case Western Reserve University, Cleveland, Ohio, United States.
Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio, United States.
Am J Physiol Cell Physiol. 2024 Jan 1;326(1):C74-C88. doi: 10.1152/ajpcell.00366.2023. Epub 2023 Nov 20.
Diversity in the functional expression of ion channels contributes to the unique patterns of activity generated in visceral sensory A-type myelinated neurons versus C-type unmyelinated neurons in response to their natural stimuli. In the present study, Kv2 channels were identified as underlying a previously uncharacterized delayed rectifying potassium current expressed in both A- and C-type nodose ganglion neurons. Kv2.1 and 2.2 appear confined to the soma and initial segment of these sensory neurons; however, neither was identified in their central presynaptic terminals projecting onto relay neurons in the nucleus of the solitary tract (nTS). Kv2.1 and Kv2.2 were also not detected in the peripheral axons and sensory terminals in the aortic arch. Functionally, in nodose neuron somas, Kv2 currents exhibited frequency-dependent current inactivation and contributed to action potential repolarization in C-type neurons but not A-type neurons. Within the nTS, the block of Kv2 currents does not influence afferent presynaptic calcium influx or glutamate release in response to afferent activation, supporting our immunohistochemical observations. On the other hand, Kv2 channels contribute to membrane hyperpolarization and limit action potential discharge rate in second-order neurons. Together, these data demonstrate that Kv2 channels influence neuronal discharge within the vagal afferent-nTS circuit and indicate they may play a significant role in viscerosensory reflex function. We demonstrate the expression and function of the voltage-gated delayed rectifier potassium channel Kv2 in vagal nodose neurons. Within sensory neurons, Kv2 channels limit the width of the broader C-type but not narrow A-type action potential. Within the nucleus of the solitary tract (nTS), the location of the vagal terminal field, Kv2 does not influence glutamate release. However, Kv2 limits the action potential discharge of nTS relay neurons. These data suggest a critical role for Kv2 in the vagal-nTS reflex arc.
离子通道功能表达的多样性导致内脏感觉 A 型有髓神经元与 C 型无髓神经元对其天然刺激产生独特的活动模式。在本研究中，Kv2 通道被鉴定为在 A 型和 C 型结状神经节神经元中表达的先前未表征的延迟整流钾电流的基础。Kv2.1 和 2.2 似乎局限于这些感觉神经元的体和起始段；然而，在投射到孤束核 (nTS) 中继神经元的中央突触前末梢中，均未鉴定到它们。Kv2.1 和 Kv2.2 也未在主动脉弓的周围轴突和感觉末梢中检测到。在结状神经元体中，Kv2 电流表现出频率依赖性电流失活，并有助于 C 型神经元而非 A 型神经元的动作电位复极化。在 nTS 内，Kv2 电流阻断不会影响传入激活时的传入突触前钙内流或谷氨酸释放，这支持我们的免疫组织化学观察结果。另一方面，Kv2 通道有助于膜超极化并限制二级神经元的动作电位放电率。总的来说，这些数据表明 Kv2 通道影响迷走传入-孤束核回路中的神经元放电，并表明它们可能在内脏感觉反射功能中发挥重要作用。我们证明了电压门控延迟整流钾通道 Kv2 在迷走结状神经元中的表达和功能。在感觉神经元中，Kv2 通道限制了较宽的 C 型而非较窄的 A 型动作电位的宽度。在孤束核 (nTS) 中，迷走神经末梢的位置，Kv2 不影响谷氨酸释放。然而，Kv2 限制了 nTS 中继神经元的动作电位放电。这些数据表明 Kv2 在迷走神经-孤束核反射弧中具有关键作用。
