Therefore, it seems that mechanisms that prevents Ca2+ influx and/or decrease Ca2+ level despite high cGMP level exist in AFD, which is consistent with our previous finding that SLO K+ channels contribute to decrement of Ca2+ level in AFD after its increment by warming [40]; both SLO-1 and SLO-2 channels are activated by Ca2+, and the resulting K+ efflux may prevent Ca2+ influx possibly by inactivating voltage-dependent Ca2+ channels. This evidence concerns the gene KCNMA1 and Nager acrofacial dysostosis.