Primary cilia TRP channel regulates hippocampal excitability.

Polycystins (PKD2, PKD2L1, and PKD2L2) are members of the transient receptor potential family, which form ciliary ion channels. Most notably, PKD2 dysregulation in the kidney nephron cilia is associated with polycystic kidney disease, but the function of PKD2L1 in neurons is undefined. In this report, we develop animal models to track the expression and subcellular localization of PKD2L1 in the brain.

Energetic landscape of polycystin channel gating.

Members of the polycystin family (PKD2 and PKD2L1) of transient receptor potential (TRP) channels conduct Ca and depolarizing monovalent cations. Variants in PKD2 cause autosomal dominant polycystic kidney disease (ADPKD) in humans, whereas loss of PKD2L1 expression causes seizure susceptibility in mice. Understanding structural and functional regulation of these channels will provide the basis for interpreting their molecular dysregulation in disease states.

Targeting the tamoxifen receptor within sodium channels to block osteoarthritic pain.

Voltage-gated sodium channels (Na) in nociceptive neurons initiate action potentials required for transmission of aberrant painful stimuli observed in osteoarthritis (OA). Targeting Na subtypes with drugs to produce analgesic effects for OA pain management is a developing therapeutic area. Previously, we determined the receptor site for the tamoxifen analog N-desmethyltamoxifen (ND-Tam) within a prokaryotic Na.