# Role of Kir4.1 Channel in Auditory Function: Impact on Endocochlear Potential and Hearing Loss
## 4 Discussion
### Kir4.1 Channel
#### 4.3.4 K+ Cochlear Cycle  
The stereocilia of hair cells are equipped with mechanosensitive channels. These channels are connected to prestin, a protein that, when mechanically stimulated, opens the K+ channels, inducing an influx of ions into the hair cell due to the large concentration gradient [44]. It should be noted that the potential in the vestibular endolymph is only about +5 mV, while as seen in the cochlea duct, it can reach up to +100 mV due to the EP. This large potential makes the cochlear hair cells much more sensitive to the opening of potassium channels. Once potassium depolarizes the cell and triggers the release of calcium ions, it exits from the basolateral portion of the hair cells through a series of channels present in the membrane such as KCNQ4 and BK in OHCs and KNCQ4, BK, and Ik5 in IHCs. When KCNQ4 is absent, cells degenerate [45]. At this point, the potassium recycling phase begins, which can be divided into two different pathways: the intraepithelial or lateral route and the extraepithelial or medial route of K+ recycling [46] (Figure 5). Figure 5: The schematic representation represents the two pathways involved in potassium recycling within the cochlea. (1) The intraepithelial or lateral route, proper for the outer hair cell (OHC), can follow three distinct pathways. The first is a non-mediated route that directly transfers potassium to the perilymph. The second pathway facilitated by Deiters’ cells is towards the perilymph. The third pathway is more complex; it involves several cell types, such as Deiters’ cells, Claudius cells, and root cells, which ultimately lead to the perilymph adjacent to fibrocytes. After that, all potassium is transported to the stria vascularis. Gap junctions (GapJ) are heavily relied upon by the third pathway. (2) The extraepithelial or medial route, which is proper for the inner hair cell (IHC), encompasses interdental cells (IDCs), inner sulcus cells (ISCs), and interphalangeal cells (IPhCs). The transport of potassium in the endolymph occurs through an interconnected network of gap junctions. The image shows the types of ion channels that reside within the aforementioned cells, including Kir channels, aquaporin-4 (AQP4), and gap junctions. The intraepithelial or lateral route, which serves as the primary potassium recycling route, warrants further examination. According to [PERSON] et al., three models could elucidate the recycling process [15]:  
* Potassium recycling through open perilymph (first pathway): The potassium efflux from the hair cells is directed into the interstitial space between the inner hair cells and supporting cells, as well as between the outer hair cells and Deiters' cells. Subsequently, potassium is introduced into the perilymph and captured by the fibrocytes of the spiral ligament without the involvement of other cells in its entry into the perilymph. * Potassium recycling buffered (second pathway): The potassium introduced into the interstitial space, released from the OHCs or IHCs, is promptly recaptured by Deiters' cells or supporting cells, which mediate its release into the perilymph. * Potassium recycling via gap junctions (third pathway): Once the IHCs or OHCs release potassium ions into the interstitial space, it is immediately recaptured by Deiters' cells and supporting cells and subsequently transported back to the stria vascularis via a dense network of gap junctions. Moreover, observational evidence suggests that, in addition to Deiters' and Claudius cells, outer sulcus cells contribute to the following factors: (1) Ionic homeostasis is maintained, as the root cells, along with other cells of the cochlear epithelium, are implicated in maintaining appropriate potassium concentrations in the perilymph and endolymph for normal auditory function. (2) There is a role in potassium \"recycling\", and in this case the root cells may participate in the \"recycling\" of potassium in the cochlear epithelium.