Abstract
Renal water reabsorption increases in pregnancy and lactation to expand maternal blood volume to cope with the cardiovascular demands of the developing fetus and new-born baby. Vasopressin (antidiuretic hormone) promotes renal water reabsorption and its secretion is principally stimulated by body fluid osmolality. Hence, lowered osmolality normally decreases vasopressin secretion. However, despite water retention profoundly reducing osmolality in pregnancy and lactation, vasopressin levels are maintained to drive blood volume expansion. Despite its importance for successful reproduction, the cellular mechanisms that maintain vasopressin secretion in the face of decreased osmolality during pregnancy and lactation are unknown. Vasopressin is secreted by neurons that are intrinsically osmosensitive through expression of N-terminal truncated-transient receptor potential vanilloid-1 channel, ΔN-TRPV1, which is mechanically activated by osmotically-induced cell shrinkage to increase vasopressin neuron activity. Vasopressin neurons also express TRPV4 but the role of TRPV4 in vasopressin neuron function is not well characterised. Here, we summarise our novel evidence showing that TRPV4 forms functional channels with ΔN-TRPV1 that have a greater single-channel conductance compared to channels with ΔN-TRPV1 alone. We propose that upregulation of TRPV4 heteromerisation with ΔN-TRPV1 might maintain vasopressin secretion in pregnancy and lactation to expand blood volume for successful reproduction.