Cloned human aquaporin-1 is a cyclic GMP-gated ion channel

Aquaporin-1 (AQP1) is a member of the membrane intrinsic protein (MIP) gene family and is known to provide pathways for water flux across cell membran es. We show here that cloned human AQP1 not only mediates water flux but al so serves as a cGMP-gated ion channel. Two-electrode voltage-clamp analyses showed consistent activation of an ionic conductance in wild-type AQP1-exp ressing oocytes after the direct injection of cGMP (50 nl of 100 mM). Curre nt activation was not observed in control (water-injected) oocytes or in AQ P5-expressing oocytes with osmotic water permeabilities equivalent to those seen with AQP1. Patch-clamp recordings revealed large conductance channels (150 pS in K+ saline) in excised patches from AQP1-expressing oocytes afte r the application of cGMP to the internal side. Amino acid sequence alignme nts between AQP1 and sensory cyclic-nucleotide-gated channels showed simila rities between the cyclic-nucleotide-gated binding domain and the AQP1 carb oxyl terminus that were not present in AQP5. Competitive radioligand-bindin g assays with [H-3]cGMP demonstrated specific binding (K-D = 0.2 mu M) in A QP1-expressing Sf9 cells but not in controls. These results indicate that A QP1 channels have the capacity to participate in ionic signaling after the activation of cGMP second-messenger pathways.