Involvement of sodium-glucose cotransporter-1 activities in maintaining oscillatory Cl - currents from mouse submandibular acinar cells.

Autor: Takeyasu M; Department of Physiology and Oral Physiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8553, Japan.; Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan., Kozai K; Department of Pediatric Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan., Sugita M; Department of Physiology and Oral Physiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8553, Japan. sugisan@hiroshima-u.ac.jp.
Jazyk: angličtina
Zdroj: Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology [J Comp Physiol B] 2024 Feb; Vol. 194 (1), pp. 21-32. Date of Electronic Publication: 2024 Feb 03.
DOI: 10.1007/s00360-024-01532-w
Abstrakt: In salivary acinar cells, cholinergic stimulation induces elevations of cytosolic [Ca 2+ ] i to activate the apical exit of Cl - through TMEM16A Cl - channels, which acts as a driving force for fluid secretion. To sustain the Cl - secretion, [Cl - ] i must be maintained to levels that are greater than the electrochemical equilibrium mainly by Na + -K + -2Cl - cotransporter-mediated Cl - entry in basolateral membrane. Glucose transporters carry glucose into the cytoplasm, enabling the cells to produce ATP to maintain Cl - and fluid secretion. Sodium-glucose cotransporter-1 is a glucose transporter highly expressed in acinar cells. The salivary flow is suppressed by the sodium-glucose cotransporter-1 inhibitor phlorizin. However, it remains elusive how sodium-glucose cotransporter-1 contributes to maintaining salivary fluid secretion. To examine if sodium-glucose cotransporter-1 activity is required for sustaining Cl - secretion to drive fluid secretion, we analyzed the Cl - currents activated by the cholinergic agonist, carbachol, in submandibular acinar cells while comparing the effect of phlorizin on the currents between the whole-cell patch and the gramicidin-perforated patch configurations. Phlorizin suppressed carbachol-induced oscillatory Cl - currents by reducing the Cl - efflux dependent on the Na + -K + -2Cl - cotransporter-mediated Cl - entry in addition to affecting TMEM16A activity. Our results suggest that the sodium-glucose cotransporter-1 activity is necessary for maintaining the oscillatory Cl - secretion supported by the Na + -K + -2Cl - cotransporter activity in real time to drive fluid secretion. The concerted effort of sodium-glucose cotransporter-1, Na + -K + -2Cl - cotransporter, and apically located Cl - channels might underlie the efficient driving of Cl - secretion in different secretory epithelia from a variety of animal species.
(© 2024. The Author(s).)
Databáze: MEDLINE
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