title: 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.
authors.affiliation: Centre for Research in Neuroscience, Montreal General Hospital and McGill University, Montreal, Quebec, Canada H3G 1A4.
authors.forename: Zizhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Alexandra N
authors.initials: AN
authors.lastname: Kindrat
authors.forename: Reza
authors.initials: R
authors.lastname: Sharif-Naeini
authors.forename: Charles W
authors.initials: CW
authors.lastname: Bourque
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology*; D000818:Animals; D015640:Ion Channel Gating / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000502:physiology*; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D020318:Rats, Long-Evans; D011984:Sensory Receptor Cells / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013495:Supraoptic Nucleus / Q000502:physiology*; D014882:Water-Electrolyte Balance / Q000502:physiology*