PKD2L1 channels segregated to the apical compartment are the dual-mode pH sensor in cerebrospinal fluid-contacting neurons

Cerebrospinal fluid-contacting neurons, also known as CSFcNs, are GABAergic cells that envelop the central canal of the spinal cord. These neurons have their soma situated sub-ependymally, and a dendritic-like process that terminates as an apical process inside the central canal. The exact relationship between this unique anatomical organization and their function as a multimodal sensor of cerebrospinal fluid composition is still not fully understood.

A crucial physiological trait of CSFcNs is a conspicuous spontaneous electrical activity driven by PKD2L1 channels, a non-selective cation channel belonging to the TRP family. These channels exhibit a high single-channel conductance, approximately 200 pS, and can be modulated by protons and mechanical forces. The researchers investigate the sensitivity of PKD2L1 channels to pH and its impact on CSFcNs excitability.

Their findings demonstrate that PKD2L1 channels not only produce phasic inward currents but also a sustained current, both of which are modulated bidirectionally by pH, showing a high sensitivity around physiological values. Through a combination of electrophysiological recordings from both intact and isolated apical processes, as well as optical methods involving laser photolysis of protons, the researchers establish that functional PKD2L1 channels are specifically localized within the apical process.

The spatial segregation of PKD2L1 channels, combined with their biophysical properties (including high single-channel conductance and pH sensitivity), and the apical process's unique membrane properties (characterized by very high input resistance), make CSFcN excitability highly responsive to modulation by PKD2L1 channels. The researchers conclude that these findings illustrate how the apical process's properties are finely tuned to effectively support the sensory role of CSFcNs.