Linz Peter, Hutter Eva, Ditting Tillmann, Schiffer Mario, Amann Kerstin, Hilgers Karl F, Veelken Roland, Rodionova Kristina
Department of Internal Medicine 4, University of Erlangen-Nürnberg, Erlangen, Germany.
Department of Pathology (Section Nephropathology), Friedrich-Alexander University Erlangen, Erlangen, Germany.
Front Physiol. 2025 Oct 8;16:1644488. doi: 10.3389/fphys.2025.1644488. eCollection 2025.
Cardiac vagal afferent neurons, located in the nodose ganglion, play a pivotal role in cardiopulmonary reflexes that link cardiac filling states to renal sympathetic outflow and the maintenance of circulatory homeostasis. Their excitability depends on a fine balance of depolarizing and repolarizing ion fluxes, yet the contribution of mechanosensitive (MS) ion channels to this regulation remains incompletely understood. While non-selective cation channels such as Piezo1/2 are established mediators of baroreceptor function, they are not directly responsible for repolarization. In contrast, mechanosensitive potassium channels are ideally suited to terminate action potentials and thereby shape afferent signaling from the heart. We, therefore, tested the hypothesis that MS potassium channels are functionally expressed in nodose ganglion neurons with cardiac projections. Using excised-patch recordings with stepwise suction, we identified two types of MS channels. One was inhibited by extracellular gadolinium (100 µM) and exhibited a higher unitary conductance, while the other was insensitive to gadolinium and showed a lower conductance. Both channel types were predominantly selective for K but also permeable to Na, with a relative K: Na permeability of ∼3.3-3.4. This mixed selectivity provides sufficient depolarization to activate voltage-gated Na channels and thereby initiate action potential firing. Our findings provide direct evidence for the presence of MS potassium channels in cardiac vagal afferent neurons and suggest that they may contribute critically to the mechanoelectric coupling and reflex control of cardiovascular function.
位于结状神经节的心脏迷走传入神经元在心肺反射中起关键作用，这种反射将心脏充盈状态与肾交感神经流出以及循环稳态的维持联系起来。它们的兴奋性取决于去极化和复极化离子通量的精细平衡，然而机械敏感（MS）离子通道对这种调节的贡献仍未完全了解。虽然诸如Piezo1/2等非选择性阳离子通道是压力感受器功能的既定介质，但它们并不直接负责复极化。相比之下，机械敏感钾通道非常适合终止动作电位，从而塑造来自心脏的传入信号。因此，我们测试了以下假设：MS钾通道在具有心脏投射的结状神经节神经元中功能性表达。使用逐步抽吸的膜片钳记录，我们鉴定出两种类型的MS通道。一种被细胞外钆（100μM）抑制，且表现出较高的单位电导，而另一种对钆不敏感，且电导较低。两种通道类型对K均具有主要选择性，但对Na也有通透性，相对K:Na通透性约为3.3 - 3.4。这种混合选择性提供了足够的去极化以激活电压门控Na通道，从而启动动作电位发放。我们的研究结果为心脏迷走传入神经元中存在MS钾通道提供了直接证据，并表明它们可能对心血管功能的机电耦合和反射控制起关键作用。
