# Role of Kir4.1 Channel in Auditory Function: Impact on Endocochlear Potential and Hearing Loss
## 4 Discussion  
### Auditory Function  
The outer ear picks up sound waves that are then transmitted through the tympanic membrane to the middle ear, where the ossicles amplify them to reach the inner ear (cochlea). The mechanical energy of waves is converted into electrical signals by the cochlear sensorial tissue [9; 10; 11; 12]. The cochlea is a spiral auditory sense organ composed of three fluid-filled compartments: the scala typpani, the scala media, and the scala vestibuli. In the scala typpani and scala vestibuli, perilymph flows exhibit higher sodium and lower potassium levels. However, in scala media, the endolymph displays a higher potassium concentration and lower levels of calcium and sodium, ensuring a positive endocochlear potential (EP) (Figure 1).  
The concentration of K\({}^{+}\) ions in the endolymph is responsible for maintaining it [13]. The vibration induced by sounds causes the stereocilia to deflect from the apical membrane of hair cells. This deflection led to the opening of the K\({}^{+}\) mechanosensitive channels located at the top of their stereocilia, which are in contact with the endolymph. The entry of endolymphatic K\({}^{+}\) into hair cells leads to their depolarization. By opening calcium channels and exocytosis glutamate neurotransmitters, mechanical signals transform into electrical transmission. The signal is directed toward the nerve endings of the auditory nerve and the nuclei of the central nervous system [9; 10; 11; 14]. The action of EP leads to an increase in sensitivity for cochlear hair cells by enhancing the potential generated on their basolateral membrane. After acoustic stimulation, the ions pass through a gap junction pathway and specific channels [9; 10; 11; 14; 15].  
It is widely documented that K\({}^{+}\) is produced from the basal region of hair cells and transported back from the perilymph to the endolymph by means of tissues of the cochlear lateral wall (including the spiral ligament and stria vascularis) [14; 16]. The spiral ligament comprises fibrocytes, while the stria vascularis is made up of two epithelial layers: one marginal cell layer and another layer consisting of intermediate and basal cells. The intragral space is the region between these two layers [13; 14; 16] (Figure 2).  
Figure 1: The cochlear anatomy and composition of fluids in the ear. The scala media is filled with the endolymph, which contains 150 mM potassium, 1 mM sodium, and almost no calcium (0.02 mM), resulting in a highly positive endocochlear potential (+80 mV). The perilymph fills the scala vestibuli and the scala typpani; similarly to the cerebrospinal fluid, it is rich in sodium (140 mM) and poor in potassium (5 mM) and calcium (1.2 mM), resulting in a potential near 0 mV.  
The circulation of potassium ions in the cochlea is believed to be mediated by five components: (1) the perilymph receives K\({}^{+}\) from hair cells through their basolateral K\({}^{+}\) channels; (2) the cells that support hair cells are responsible for absorbing K\({}^{+}\); (3) epithelial cells on the basilar membrane; (4) the spiral ligament; (5) the stria vascularis. Finally, potassium is released into the endolymphatic fluid through marginal cells of the stria vascularis [14]. Recent studies have demonstrated that each component has its own set of ion transport devices and plays a specific role in the cochlear circulation of K\({}^{+}\). When potassium recycling is interrupted, it results in decreased EP, which ultimately leads to deafness [14].