Mechanism of H+ and Cl− secretion by an activated parietal cell in the gastric mucosa. ATP, adenosine triphosphate.
and are connected by a common outlet to the cell’s luminal surface. Microvilli line the surfaces of the secretory canaliculi. The cytoplasm of unstimulated parietal cells contains numerous tubules and vesicles called the tubulovesicular system. The membranes of tubulovesicles contain the transport proteins responsible for secretion of H+ and Cl− into the lumen of the gland. When parietal cells are stimulated to secrete HCl (see
Fig. 29.3 ), tubulovesicular membranes fuse with the plasma membrane of the secretory canaliculi. This extensive membrane fusion greatly increases the number of H+/K+ antiporters in the plasma membrane of the secretory canaliculi. When parietal cells secrete gastric acid at the maximal rate, H+ is pumped against a concentration gradient that is about 1 million–fold. Thus the pH is 7 in the parietal cell cytosol and 1 in the lumen of the gastric gland.
The cellular mechanism of H+ secretion by the parietal cell is depicted in
Fig. 29.4 . Cl− enters the cell across the basolateral membrane in exchange for HCO3 − generated in the cell by the action of carbonic anhydrase, which produces HCO3 − and H+ . H+ is secreted across the luminal membrane by H+,K+-ATPase in exchange for K+ . K+ recycles across the luminal membrane via a K+ channel. Cl− enters the lumen via an ion channel (a CLC family Cl− channel) located in the luminal membrane. Increased intracellular Ca++ and cyclic adenosine monophosphate (cAMP) stimulate luminal membrane conduction of Cl− and K+ . Increased K+ conductance hyperpolarizes the luminal membrane
CHAPTER 29 The Gastric Phase of the Integrated Response to a Meal 533 potential, which increases the driving force for efflux of Cl− across the luminal membrane. The K+ channel in the basolateral membrane also mediates the efflux of K+ that accumulates in the parietal cell via the activity of H+,K+-ATPase. In addition, cAMP and Ca++ promote trafficking of Cl− channels into the luminal membrane, as well as fusion of cytosolic tubulovesicles containing H+,K+-ATPase with the membrane of the secretory canaliculi (see
Figs. 29.3 29.4 ). Parietal cell secretion of H+ is also accompanied by transport of HCO3 − into the bloodstream to maintain intracellular pH.
Secretion of HCO3 −
The surface epithelial cells also secrete a watery fluid that contains Na+ and Cl− in concentrations similar to those in plasma but with higher K+ and HCO3 − concentrations. HCO3 − is entrapped by the viscous mucus that coats the surface of the stomach; thus the mucus secreted by the resting mucosa lines the stomach with a sticky alkaline coat. When food is eaten, rates of secretion of both mucus and HCO3 − increase.
Secretion of Mucus
Secretions that contain mucins are viscous and sticky and are collectively termed mucus. Mucins are secreted by mucous neck cells located in the necks of gastric glands and by the surface epithelial cells of the stomach. Mucus is stored in large granules in the apical cytoplasm of mucous neck cells and surface epithelial cells and is released by exocytosis.
Gastric mucins are about 80% carbohydrate by weight and consist of four similar monomers of about 500,000 Da each that are linked together by disulfide bonds (Fig. 29.5