Although a direct regulatory effect of S1P3 on potassium channel activity is not supported by the present results, this leaves three alternative possibilities as explanations for the significantly reduced input resistance and firing frequency in S1P3−/− mice: first, other members of the large potassium channel family may be targeted by S1P3 receptor signaling similar to a study in human anaplastic thyroid cancer cells where S1P down-regulates Kv11.1 regulation via S1P2 (Asghar et al., 2012). This evidence concerns the gene S1PR2 and thyroid gland undifferentiated (anaplastic) carcinoma.