Figure 2.

Disruption of the epidermal Ca²⁺ gradient by mutant Cx26 hemichannels in KID syndrome. (A). Cx26 KID mutant hemichannels have a higher net flux of Ca²⁺ and broader expression pattern than wild-type Cx26. (B). In normal epidermis, Cx26 is restricted to cells in the basal layer, and there is a gradient of Ca²⁺ with the highest levels in the granular layer, and low levels in the basal layer. In KID epidermis, mutant Cx26 expression expands across the epithelium, increasing Ca²⁺ flux and eliminating the normal Ca²⁺ gradient. The loss of the Ca²⁺ gradient disrupts the normal regulation of keratinocyte proliferation (favored in low Ca²⁺) and differentiation (favored in high Ca²⁺) resulting in a greatly thickened epidermis and a decrease in differentiated cells.