# Role of Kir4.1 Channel in Auditory Function: Impact on Endocochlear Potential and Hearing Loss
## 4 Discussion
### Kir4.1 Channel
#### 4.3.2 Embryonal and Postnatal Development  
Several authors reported that in the stria vascularis, KCNJ10 is the only Kir channel expressed in intermediate cells [11; 35; 36]. The development of intermediate cells shows that KCNJ10 channels play a functional role in the formation of the endocochlear potential, as indicated by the time course of KCNJ10 expression in the rat model [11]. The cochlear lateral wall is where Kir4.1 expression is developed and it is linked to the generation of EP in the inner ear, as is stated in the literature. This can be inferred from both the gradual positivity of EP and the increase in the ion potassium concentration in the endolymph after birth [28]. Kir4.1 was the only member of the Kir channel family in the rat animal model that has been specifically identified in the basolateral membrane of marginal cells, not base or intermediate cells [28]. The Kir4.1 immunoreactivity was not observed from postnatal day 1 (P1) to P5 in rats [28]. Similar results were reported in mice deficient in H+-ATPase, when the stria vascularis is still in an immature state and no EP can be recorded [35]. At P8, the endolymphatic [K+] level reaching the adult positive level leads to a weak Kir4.1 immunoreactivity in the stria vascularis, which then progresses to a positive EP (it is noteworthy that the immunoreactivity appeared simultaneously in all turns of the cochlea in the stria vascularis). Kir4.1's expression increased rapidly during the next few days, peaking at P14 when it exhibits a high expression, similar to that of adult rats. Furthermore, Kir4.1 developmental expression in satellite cells surrounding ganglion neurons appears to be equivalent to that in marginal cells [28]. The authors conclude that Kir4.1's time course is closely associated with EP elevation, but not endolymphatic-wise [K+], which implies that Kir4.1 is involved in EP generation [28] (Figure 3). The expression of potassium channels was also investigated in human fetal cochleae during week 9 to week 18 (W9-W18) [7]. The sodium-potassium pump Na+/K+ATPase was found to be positive in the cochlear duct epithelium at W10 and exhibited an increase in expression in the lateral wall epithelium at W12. In parallel, KCNQ1 appeared at W10 and W12 in the epithelium of the lateral wall of the basement membrane. It is noteworthy that at W12, melanocytes that derive from the neural crest migrated into the cochlea and reached the basement membrane of the lateral wall epithelium, becoming intermediate cells of the stria vascularis. In the following two weeks, the positivity of sodium-potassium pump expression was extended to marginal cells, the inner and outer hair cells, and epithelial cellsin the outer sulcus, while KCNQ1 became expressed in the Reissner's membrane and the outer sulcus cells, and at W16, also to the marginal cells. In parallel, the SLC2A1 channel, responsible for the expression of GLUT1, was detectable from W12 to W18 in the apical membrane of epithelial cells between the organ of Corti and the outer sulcus root cells. The developmental expression of KCNQ1 and the sodium-potassium pump Na\({}^{+}\)/K\({}^{+}\)ATPase suggests that both K\({}^{+}\) uptake and secretion could be mediated by marginal cells as early as W16-W18 [7]. KCNJ10, or Kir4.1, plays a significant role in the ability of stria vascularis melanocytes to release K\({}^{+}\) ions into the intragrial space and contribute to the generation of EP. Its expression in melanocytes did not occur until the last stage of the investigation of W18; in addition, it took from W16 to W18 to become expressed in the epithelial cells of the outer sulcus, including root cells (Figure 3). From W14 to W18, the gap junction proteins GJB2/CX26 and GJB6/CX30 were also expressed in the cells in the outer sulcus, but not in the spiral ligament. These two pieces of evidence suggest that it is likely that the EP has not yet been generated at this stage [7].