The Osmotic Control of Vasopressin‐Releasing Neurons

Vasopressin is a neurohypophysial hormone which plays a key role in central osmoregulation. Activation of vasopressin receptors expressed by kidney cells induces an increase in water reabsorption, effectively reducing water loss. Circulating levels of vasopressin are largely determined by the rate of action potential firing by magnocellular neurosecretory cells, which synthesize and secrete the hormone. These neurons are found in two sets of bilaterally located hypothalamic nuclei, namely the supraoptic and paraventricular nuclei. The action potential firing rate of magnocellular neurosecretory cells has been shown to be directly correlated to plasma osmolality. This property of magnocellular neurosecretory cells arises from changes in excitability resulting from (i) synaptic inputs from central osmosensor regions and other brain areas that receive osmosensitive inputs, (ii) osmosensitive release of transmitter from neighboring astrocytes, and (iii) activation of mechanosensitive channels that allow these neurons to intrinsically sense changes in external osmolality. This chapter features a detailed discussion of each of these three levels of osmosensitive regulation: discovery, mechanisms of osmosensitivity, and how they modulate the firing activity of magnocellular neurosecretory neurons.