An activated parietal cell in the gastric mucosa secretes H+ and Cl- through a mechanism involving ATP. The cell's luminal surface is connected to both H+ and Cl- outlets. Microvilli line the surfaces of the secretory canaliculi, and the cytoplasm of unstimulated parietal cells contains tubules and vesicles called the tubulovesicular system. These tubulovesicles contain transport proteins responsible for H+ and Cl- secretion into the gland's lumen.

When parietal cells are stimulated to secrete HCl, the tubulovesicular membranes fuse with the plasma membrane of the secretory canaliculi, increasing the number of H+/K+ antiporters in the plasma membrane. During maximal secretion of gastric acid, H+ is pumped against a concentration gradient that is approximately 1 million-fold. Consequently, the pH is 7 in the parietal cell cytosol and 1 in the lumen of the gastric gland.

The cellular mechanism of H+ secretion involves Cl- entering the parietal cell through the basolateral membrane, exchanged for HCO3- generated within the cell by carbonic anhydrase. H+ is then secreted across the luminal membrane via H+,K+-ATPase in exchange for K+. K+ is recycled across the luminal membrane through a K+ channel. Cl- enters the lumen through an ion channel located in the luminal membrane.

Increased intracellular Ca++ and cyclic adenosine monophosphate (cAMP) stimulate the conduction of Cl- and K+ across the luminal membrane. Increased K+ conductance hyperpolarizes the luminal membrane potential, enhancing the efflux of Cl- across the luminal membrane. The K+ channel in the basolateral membrane also facilitates the efflux of K+ accumulated in the parietal cell through the activity of H+,K+-ATPase. Additionally, cAMP and Ca++ promote the trafficking of Cl- channels into the luminal membrane, as well as the fusion of cytosolic tubulovesicles containing H+,K+-ATPase with the secretory canaliculi membrane.

H+ secretion by parietal cells is accompanied by the transport of HCO3- into the bloodstream to maintain intracellular pH.

In addition to HCO3-, the surface epithelial cells secrete a watery fluid that contains Na+ and Cl-, with higher concentrations of K+ and HCO3-. The alkaline mucus secreted by the resting mucosa lines the stomach and entraps HCO3-. When food is consumed, secretion rates of mucus and HCO3- increase.

Mucus, which contains mucins, is a viscous and sticky secretion produced by mucous neck cells located in the necks of gastric glands and 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 it is released through exocytosis.

Gastric mucins are primarily composed of carbohydrates, making up about 80% of their weight. They consist of four similar monomers, each weighing approximately 500,000 Da, which are linked together by disulfide bonds.
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