Actin Filaments Mediate Mechanical Gating during Osmosensory Transduction in Rat Supraoptic Nucleus Neurons

Abstract

Osmosensory transduction is a bidirectional process displayed by neurons involved in the control of thirst and antidiuretic hormone release, and is therefore crucial for body fluid homeostasis. Although this mechanism is known to involve the activation of nonselective cation channels during hypertonicity-evoked shrinking, and the inhibition of these channels during hypotonicity-evoked swelling, the basis for this regulation is unknown. Here, we investigated this process using whole-cell patch-clamp recordings from neurons acutely isolated from the supraoptic nucleus of adult rats. The mechanosensitivity index, defined as the ratio of conductance change to normalized volume change, was quantitatively equivalent whether cell volume was increased or decreased by changes in extracellular fluid osmolality, or by changes in pipette pressure. Moreover, responses induced by hyperosmotic or hypo-osmotic media could be reversed by increasing or decreasing pipette pressure, respectively. The mechanosensitivity index was significantly reduced in neurons treated with cytochalasin-D, a compound that promotes the depolymerization of actin filaments. Conversely, cells treated with jasplakinolide, a compound that promotes actin polymerization, showed a significant increase in mechanosensitivity index. Finally, the depolarizing and excitatory effects of hypertonic stimuli were significantly enhanced by jasplakinolide and reduced by cytochalasin-D. We conclude that osmosensory transduction in these neurons is a reversible mechanical process that depends on an intact actin cytoskeleton, and the sensitivity of the transducer appears to vary in proportion with the density of actin filaments.

Diabetes Insipidus: A Review

“…These TRPV1 channels, in response to MNC shrinkage due to hyperosmolality, allow activation of a cation current (Ca 2+ and nonspecific monovalent cations), leading to increased action potential firing, resulting in ADH release [8][9][10]. Actin filaments are also required for the regulation of the TRPV1 channel activity, though the exact function is unknown [8,11,12]. Regulation of ADH secretion is both pre and post transcriptional.…”

Hypertonicity Sensing in Organum Vasculosum Lamina Terminalis Neurons: A Mechanical Process InvolvingTRPV1But NotTRPV4

“…Since many types of ion channels are regulated by specific solutes (e.g., Cukkemane et al, 2011) or ionic strength (e.g., Nilius et al, 2000), osmosensing could in principle be mediated by osmotically induced changes in solute concentration. Alternately, OVLT neurons might detect hypertonicity through a mechanical effect linked to shrinking, as observed in neurohypophysial neurons of the supraoptic nucleus (Zhang et al, 2007). Clarification of the cellular mechanism responsible for hypertonicity sensing in OVLT neurons is a prerequisite for our understanding of the molecular architecture and function of the mammalian osmoreceptor.…”

Diabetes insipidus: the basic and clinical review

“…25,26 The other drugs characterized as the causing agents of NDI are Amphotericin B, Colchicines, Gentamicin, Methoxyflurane and Demaclocycline. 27,28 Acquired causes also include chronic renal failure, pyelonephritis, polycystic kidney disease, renal transplantation, obstructive uropathy, chronic renal medullary disease, chronic hypokalemia and chronic hypercalcemia. 29 Low protein diets also downregulate the AQP2 protein.…”