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Unique Organization of Actin Cytoskeleton in Magnocellular Vasopressin Neurons in Normal Conditions and in Response to Salt-Loading.

ABSTRACT: Magnocellular neurosecretory cells (MNCs) are intrinsically osmosensitive and can be activated by increases in blood osmolality, triggering the release of antidiuretic hormone vasopressin (VP) to promote water retention. Hence, the activity of magnocellular VP neurons is one of the key elements contributing to the regulation of body fluid homeostasis in healthy organisms. Chronic exposure to high dietary salt leads to excessive activation of VP neurons, thereby elevating levels of circulating VP, which can cause increases in blood pressure contributing to salt-dependent hypertension. However, the molecular basis underlying high-salt diet-induced hyperactivation of magnocellular VP neurons remains not fully understood. Previous studies suggest that magnocellular neurosecretory neurons contain a subcortical layer of actin filaments and pharmacological stabilization of this actin network potentiates osmotically-induced activation of magnocellular neurons. Using super-resolution imaging in situ, we investigated the organization of the actin cytoskeleton in rat MNCs under normal physiological conditions and after a chronic increase in blood osmolality following 7?d of salt-loading (SL). We found that, in addition to the subcortical layer of actin filaments, magnocellular VP neurons are endowed with a unique network of cytoplasmic actin filaments throughout their somata. Moreover, we revealed that the density of both subcortical and cytoplasmic actin networks in magnocellular VP neurons is dramatically increased following SL. These results suggest that increased osmo-responsiveness of VP neurons following chronic exposure to high dietary salt may be mediated by the modulation of unique actin networks in magnocellular VP neurons, possibly contributing to elevated blood pressure in this condition.

SUBMITTER: Barad Z

PROVIDER: S-EPMC7189486 | biostudies-literature | 2020 Mar/Apr

REPOSITORIES: biostudies-literature

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Unique Organization of Actin Cytoskeleton in Magnocellular Vasopressin Neurons in Normal Conditions and in Response to Salt-Loading.

Barad Zsuzsanna Z Jacob-Tomas Suleima S Sobrero Alberto A Lean Graham G Hicks Amirah-Iman AI Yang Jieyi J Choe Katrina Y KY Prager-Khoutorsky Masha M

eNeuro 20200301 2

Magnocellular neurosecretory cells (MNCs) are intrinsically osmosensitive and can be activated by increases in blood osmolality, triggering the release of antidiuretic hormone vasopressin (VP) to promote water retention. Hence, the activity of magnocellular VP neurons is one of the key elements contributing to the regulation of body fluid homeostasis in healthy organisms. Chronic exposure to high dietary salt leads to excessive activation of VP neurons, thereby elevating levels of circulating VP ...[more]

PMID: 32209611

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Project description:Salt-loading (SL) impairs GABAA inhibition of arginine vasopressin (AVP) neurones in the supraoptic nucleus (SON) of the hypothalamus. Based on previous studies, we hypothesised that SL activates tyrosine receptor kinase B (TrkB), down-regulating the activity of K+ /Cl- co-transporter2 (KCC2) and up-regulating Na+ /K+ /Cl- co-transporter1 (NKCC1). These changes in chloride transport would result in increased [Cl- ]i in SON AVP neurones. The study combined virally-mediated chloride imaging with ClopHensorN with a single-cell western blot analysis. An adeno-associated virus with ClopHensorN and a vasopressin promoter (AAV2-0VP1-ClopHensorN) was bilaterally injected in the SON of adult male Sprague-Dawley rats that were either euhydrated (Eu) or salt-loaded (SL) for 7 days. Acutely dissociated SON neurones expressing ClopHensorN were tested for decreases or increases in [Cl- ]i in response to focal application of the GABAA agonist muscimol (100 ?mol L-1 ). SON AVP neurones from Eu rats showed muscimol-induced chloride influx (P < 0.05;23/35). SON AVP neurones from SL rats either significantly increased chloride efflux (P < 0.05;27/39) or did not change chloride flux (12/39). The SON AVP neurones that responded to muscimol appeared to be viable and expressed KCC2 and ?-actin. Neurones that did not respond during chloride imaging did not show KCC2 and ?-actin protein expression. The KCC2 antagonist (VU0240551,10 ?mol L-1 ) significantly blocked the chloride influx in cells from Eu rats but did not affect cells from SL rats. A NKCC1 antagonist (bumetanide,10 ?mol L-1 ) significantly blocked the chloride efflux in cells from SL rats but had no effect on cells from Eu rats. Blocking NKCC1 using bumetanide had less of an effect on the muscimol-induced Cl- influx in Eu rat neurones compared to the KCC2 antagonist. The TrkB antagonist (AnA-12) (50 ?mol L-1 ) and protein kinase inhibitor (K252a) (100 nmol L-1 ) each significantly blocked chloride efflux in SON AVP neurones from SL rats. Salt-loading increases [Cl- ]i in SON AVP neurones via a TrKB-KCC2-NKCC1-dependent mechanism in rats.

Dataset Information

Unique Organization of Actin Cytoskeleton in Magnocellular Vasopressin Neurons in Normal Conditions and in Response to Salt-Loading.

Publications

Unique Organization of Actin Cytoskeleton in Magnocellular Vasopressin Neurons in Normal Conditions and in Response to Salt-Loading.

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