Involvement of connexin43 in the acute hyperosmotic stimulus-induced synthesis and release of vasopressin in the supraoptic nucleus of rats

Abstract

Abstract. There is evidence that astroglial connexin43 (Cx43) in the supraoptic nucleus (SON) is required for the hyperosmolarity-induced increase in Fos protein expression in magnocellular neurosecretory cells (MNCs). In the present study, the role of astroglial Cx43 in the synthesis and release of vasopressin (VP) by MNCs in the SON subjected to hyperosmotic stimulus was examined. The results revealed that the VP levels in the SON and plasma were increased following acute hyperosmotic stimulus. Treatment of MNCs with Cx43-specific antisense oligodeoxynucleotides (ASODN), which temporarily reduced Cx43 protein production, limited the VP synthesis and release induced by a hyperosmotic stimulus. Similarly, the addition of gap junction and Cx43 hemichannel blockers also attenuated the VP synthesis and release induced by an acute hyperosmotic stimulus. A high extracellular [Ca 2+ ]( [Ca 2+ ] o ) has been demonstrated to reduce the gap junction activity or opening probability of Cx54 hemichannels. Notably, it was identified that high [Ca 2+ ] o attenuated the VP synthesis and release induced by acute hyperosmotic stimulus, while low [Ca 2+ ] o had a weak or no effect. These results suggested that Cx43 participates in the VP synthesis and release induced by hyperosmotic stimulation in the SON.

Role of Connexin 36 in Autoregulation of Oxytocin Neuronal Activity in Rat Supraoptic Nucleus

“…Previous studies have revealed the presence of Cx32 in SON neurons and Cx43 in SON astrocytes (Micevych et al., 1996). VP synthesis and release induced by hyperosmotic stimulation depend on increased expression of Cx43 and its function in the SON (Jiang et al., 2014). In this study, we provide the evidence of Cx36 presence in SON neurons based on studies using immunohistochemistry, Western blotting, and electrophysiology, thereby allowing a new venue to explore the biological functions of gap junctions.…”

Extracellular Cysteines Are Critical to Form Functional Cx46 Hemichannels

“…In consequence, hemichannels mediate the release of signaling molecules from cells such as ATP [6], glutamate [7], reduced glutathione (GSH) [8,9], and nicotinamide adenine dinucleotide (NAD + ) [10] as well as the uptake of glucose [11] and Ca 2+ [12]. Due to their permeability to second messengers and metabolites, hemichannels participate in relevant physiological functions, such as the formation of short-term memory [13], memory consolidation [14], gliotransmitter release [15], retina function [16], bone-hormone response and healing [17,18], neuronal-network activity [19], vasopressin synthesis and release [20], CO 2 sensing [21], etc. Despite these roles, it is well known that hemichannels present a low open probability under physiological conditions [22], which is greatly increased under pathological conditions [23,24] including metabolic stress [25], ischemia [26], inflammation [11], deafness [27], X-linked Charcot-Marie-Tooth disease [28], and skin diseases [29].…”