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Molecular basis of potassium channels in pancreatic duct epithelial cells.

Hayashi M, Novak I - Channels (Austin) (2013)

Bottom Line: In pancreatic ducts, K(+) channels hyperpolarize the membrane potential and provide the driving force for anion secretion.We will give an overview of K(+) channels with respect to their electrophysiological and pharmacological characteristics and regulation, which we know from other cell types, preferably in epithelia, and, where known, their identification and functions in pancreatic ducts and in adenocarcinoma cells.We conclude by pointing out some outstanding questions and future directions in pancreatic K(+) channel research with respect to the physiology of secretion and pancreatic pathologies, including pancreatitis, cystic fibrosis, and cancer, in which the dysregulation or altered expression of K(+) channels may be of importance.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology; University of Copenhagen; Copenhagen, Denmark.

ABSTRACT
Potassium channels regulate excitability, epithelial ion transport, proliferation, and apoptosis. In pancreatic ducts, K(+) channels hyperpolarize the membrane potential and provide the driving force for anion secretion. This review focuses on the molecular candidates of functional K(+) channels in pancreatic duct cells, including KCNN4 (KCa 3.1), KCNMA1 (KCa 1.1), KCNQ1 (Kv 7.1), KCNH2 (Kv 11.1), KCNH5 (Kv 10.2), KCNT1 (KCa 4.1), KCNT2 (KCa 4.2), and KCNK5 (K 2P 5.1). We will give an overview of K(+) channels with respect to their electrophysiological and pharmacological characteristics and regulation, which we know from other cell types, preferably in epithelia, and, where known, their identification and functions in pancreatic ducts and in adenocarcinoma cells. We conclude by pointing out some outstanding questions and future directions in pancreatic K(+) channel research with respect to the physiology of secretion and pancreatic pathologies, including pancreatitis, cystic fibrosis, and cancer, in which the dysregulation or altered expression of K(+) channels may be of importance.

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Figure 1. Model of ion transport in a pancreatic duct cell. Intracellular HCO3– is derived from CO2 through the action of carbonic anhydrase (CA) and from HCO3– uptake via the Na+–HCO3– cotransporter. H+ is extruded at the basolateral membrane by the Na+–H+ exchanger and H+–K+ pump. HCO3– efflux across the luminal membrane is mediated by Cl––HCO3– exchangers and/or Cl– channels, and the H+–K+ pump may provide a buffering/protection zone for the alkali-secreting epithelium. K+ channels provide an exit pathway for K+ and play a vital role in maintaining the membrane potential, which is a crucial component of the driving force for anion secretion.
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Figure 1: Figure 1. Model of ion transport in a pancreatic duct cell. Intracellular HCO3– is derived from CO2 through the action of carbonic anhydrase (CA) and from HCO3– uptake via the Na+–HCO3– cotransporter. H+ is extruded at the basolateral membrane by the Na+–H+ exchanger and H+–K+ pump. HCO3– efflux across the luminal membrane is mediated by Cl––HCO3– exchangers and/or Cl– channels, and the H+–K+ pump may provide a buffering/protection zone for the alkali-secreting epithelium. K+ channels provide an exit pathway for K+ and play a vital role in maintaining the membrane potential, which is a crucial component of the driving force for anion secretion.

Mentions: Potassium channels (K+ channels) are very important membrane proteins present in every cell. They determine the cell membrane potential and thereby regulate the excitability of neurons and myocytes and transport of ions and water in epithelia, such as the pancreas and salivary glands. Duct epithelial cells in the pancreas secrete a HCO3–-rich pancreatic juice that neutralizes acid chyme in the duodenum. Secretin, acetylcholine, and ATP stimulate fluid secretion via signal transduction involving cAMP and Ca2+ signaling pathways. The generally accepted model for HCO3– transport involves Cl––HCO3– exchangers (SLC26A3 and SLC26A6) that operate in parallel with cAMP-activated Cl– channels (CFTR) or Ca2+-activated Cl– channels (most likely TMEM16A) on the luminal membrane and Na+-coupled transporters such Na+–K+–Cl– co-transporter (NKCC1), Na+–HCO3– co-transporter (SLC4A4), and Na+–H+ exchanger (SLC9A1) and Na+–K+-pump on the basolateral membrane (Fig. 1).1-3 In addition, H+–K+-pumps are expressed on the luminal and basolateral membranes of pancreatic ducts.4 K+ channels are clearly important for setting the resting membrane potential and providing the driving force for anion exit and fluid secretion in a stimulated epithelium.1-3,5 K+ channels may also provide the transport partners for H+–K+-pumps.4 In addition, certain K+ channels could play an important role in pancreatic pathology, such as cystic fibrosis, pancreatitis, and pancreatic adenocarcinoma. Perhaps surprisingly, there are not so many K+ channels studies performed on pancreatic ducts.


Molecular basis of potassium channels in pancreatic duct epithelial cells.

Hayashi M, Novak I - Channels (Austin) (2013)

Figure 1. Model of ion transport in a pancreatic duct cell. Intracellular HCO3– is derived from CO2 through the action of carbonic anhydrase (CA) and from HCO3– uptake via the Na+–HCO3– cotransporter. H+ is extruded at the basolateral membrane by the Na+–H+ exchanger and H+–K+ pump. HCO3– efflux across the luminal membrane is mediated by Cl––HCO3– exchangers and/or Cl– channels, and the H+–K+ pump may provide a buffering/protection zone for the alkali-secreting epithelium. K+ channels provide an exit pathway for K+ and play a vital role in maintaining the membrane potential, which is a crucial component of the driving force for anion secretion.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4042478&req=5

Figure 1: Figure 1. Model of ion transport in a pancreatic duct cell. Intracellular HCO3– is derived from CO2 through the action of carbonic anhydrase (CA) and from HCO3– uptake via the Na+–HCO3– cotransporter. H+ is extruded at the basolateral membrane by the Na+–H+ exchanger and H+–K+ pump. HCO3– efflux across the luminal membrane is mediated by Cl––HCO3– exchangers and/or Cl– channels, and the H+–K+ pump may provide a buffering/protection zone for the alkali-secreting epithelium. K+ channels provide an exit pathway for K+ and play a vital role in maintaining the membrane potential, which is a crucial component of the driving force for anion secretion.
Mentions: Potassium channels (K+ channels) are very important membrane proteins present in every cell. They determine the cell membrane potential and thereby regulate the excitability of neurons and myocytes and transport of ions and water in epithelia, such as the pancreas and salivary glands. Duct epithelial cells in the pancreas secrete a HCO3–-rich pancreatic juice that neutralizes acid chyme in the duodenum. Secretin, acetylcholine, and ATP stimulate fluid secretion via signal transduction involving cAMP and Ca2+ signaling pathways. The generally accepted model for HCO3– transport involves Cl––HCO3– exchangers (SLC26A3 and SLC26A6) that operate in parallel with cAMP-activated Cl– channels (CFTR) or Ca2+-activated Cl– channels (most likely TMEM16A) on the luminal membrane and Na+-coupled transporters such Na+–K+–Cl– co-transporter (NKCC1), Na+–HCO3– co-transporter (SLC4A4), and Na+–H+ exchanger (SLC9A1) and Na+–K+-pump on the basolateral membrane (Fig. 1).1-3 In addition, H+–K+-pumps are expressed on the luminal and basolateral membranes of pancreatic ducts.4 K+ channels are clearly important for setting the resting membrane potential and providing the driving force for anion exit and fluid secretion in a stimulated epithelium.1-3,5 K+ channels may also provide the transport partners for H+–K+-pumps.4 In addition, certain K+ channels could play an important role in pancreatic pathology, such as cystic fibrosis, pancreatitis, and pancreatic adenocarcinoma. Perhaps surprisingly, there are not so many K+ channels studies performed on pancreatic ducts.

Bottom Line: In pancreatic ducts, K(+) channels hyperpolarize the membrane potential and provide the driving force for anion secretion.We will give an overview of K(+) channels with respect to their electrophysiological and pharmacological characteristics and regulation, which we know from other cell types, preferably in epithelia, and, where known, their identification and functions in pancreatic ducts and in adenocarcinoma cells.We conclude by pointing out some outstanding questions and future directions in pancreatic K(+) channel research with respect to the physiology of secretion and pancreatic pathologies, including pancreatitis, cystic fibrosis, and cancer, in which the dysregulation or altered expression of K(+) channels may be of importance.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology; University of Copenhagen; Copenhagen, Denmark.

ABSTRACT
Potassium channels regulate excitability, epithelial ion transport, proliferation, and apoptosis. In pancreatic ducts, K(+) channels hyperpolarize the membrane potential and provide the driving force for anion secretion. This review focuses on the molecular candidates of functional K(+) channels in pancreatic duct cells, including KCNN4 (KCa 3.1), KCNMA1 (KCa 1.1), KCNQ1 (Kv 7.1), KCNH2 (Kv 11.1), KCNH5 (Kv 10.2), KCNT1 (KCa 4.1), KCNT2 (KCa 4.2), and KCNK5 (K 2P 5.1). We will give an overview of K(+) channels with respect to their electrophysiological and pharmacological characteristics and regulation, which we know from other cell types, preferably in epithelia, and, where known, their identification and functions in pancreatic ducts and in adenocarcinoma cells. We conclude by pointing out some outstanding questions and future directions in pancreatic K(+) channel research with respect to the physiology of secretion and pancreatic pathologies, including pancreatitis, cystic fibrosis, and cancer, in which the dysregulation or altered expression of K(+) channels may be of importance.

Show MeSH
Related in: MedlinePlus