Muscarinic activation of Na+-dependent ion transporters and modulation by bicarbonate in rat submandibular gland acinus

Eun Lee Ji, Hyun Nam Joo, Sungjoon Kim

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10 Citations (Scopus)

Abstract

To investigate the interaction between the ion channels and transporters in the salivary fluid secretion, we measured the membrane voltage (Vm) and intracellular concentrations of Ca2+, Na+ ([Na +]c), Cl-, and H+ (pHi) in rat submandibular gland acini (RSMGA). After a transient depolarization induced by a short application of acetylcholine (ACh; 5 μM, 20 s), RSMGA showed strong delayed hyperpolarization (Vh,ACh; -95 ± 1.8 mV) that was abolished by ouabain. In the HCO3--free condition, the Vh,ACh was also blocked by bumetanide, a blocker of Na+-K+-2Cl- cotransporter (NKCC). In the presence of HCO3- (24 meq, bubbled with 5% CO 2), however, the Vh,ACh was not blocked by bumetanide, but it was suppressed by ethylisopropylamiloride (EIPA), a Na+/H + exchanger (NHE) inhibitor. Similarly, the ACh-induced increase in [Na+]c was totally blocked by bumetanide in the absence of HCO3-, but only by one-half in the presence of HCO 3-. ACh induced a prominent acidification of pH i in the presence of HCO3-, and the acidification was further increased by EIPA treatment. Without HCO 3-, an application of ACh strongly accelerated the NKCC activity that was measured from the decay of pHi during the application of NH4+ (20 mM). Notably, the ACh-induced activation of NKCC was largely suppressed in the presence of HCO 3-. In summary, the ACh-induced anion secretion in RSMGA is followed by the activation of NKCC and NHE, resulting an increase in [Na +]c. The intracellular Na+-induced activation of electrogenic Na+/K+-ATPase causes Vh,ACh. The regulation of NKCC and NHE by ACh is strongly affected by the physiological level of HCO3-.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume288
Issue number4 51-4
DOIs
StatePublished - 1 Apr 2005

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Bumetanide
Sodium-Hydrogen Antiporter
Submandibular Gland
Bicarbonates
Cholinergic Agents
Ions
Fluids and Secretions
Ouabain
Carbon Monoxide
Ion Channels
Acetylcholine
Anions
Adenosine Triphosphatases
Membranes
ethylisopropylamiloride

Keywords

  • Acetylcholine
  • Membrane voltage
  • Na /H exchanger
  • Na-K-2Cl cotransporter
  • Secretion

Cite this

@article{5fa159fb3fea4c6b91e3b8636cb244e3,
title = "Muscarinic activation of Na+-dependent ion transporters and modulation by bicarbonate in rat submandibular gland acinus",
abstract = "To investigate the interaction between the ion channels and transporters in the salivary fluid secretion, we measured the membrane voltage (Vm) and intracellular concentrations of Ca2+, Na+ ([Na +]c), Cl-, and H+ (pHi) in rat submandibular gland acini (RSMGA). After a transient depolarization induced by a short application of acetylcholine (ACh; 5 μM, 20 s), RSMGA showed strong delayed hyperpolarization (Vh,ACh; -95 ± 1.8 mV) that was abolished by ouabain. In the HCO3--free condition, the Vh,ACh was also blocked by bumetanide, a blocker of Na+-K+-2Cl- cotransporter (NKCC). In the presence of HCO3- (24 meq, bubbled with 5{\%} CO 2), however, the Vh,ACh was not blocked by bumetanide, but it was suppressed by ethylisopropylamiloride (EIPA), a Na+/H + exchanger (NHE) inhibitor. Similarly, the ACh-induced increase in [Na+]c was totally blocked by bumetanide in the absence of HCO3-, but only by one-half in the presence of HCO 3-. ACh induced a prominent acidification of pH i in the presence of HCO3-, and the acidification was further increased by EIPA treatment. Without HCO 3-, an application of ACh strongly accelerated the NKCC activity that was measured from the decay of pHi during the application of NH4+ (20 mM). Notably, the ACh-induced activation of NKCC was largely suppressed in the presence of HCO 3-. In summary, the ACh-induced anion secretion in RSMGA is followed by the activation of NKCC and NHE, resulting an increase in [Na +]c. The intracellular Na+-induced activation of electrogenic Na+/K+-ATPase causes Vh,ACh. The regulation of NKCC and NHE by ACh is strongly affected by the physiological level of HCO3-.",
keywords = "Acetylcholine, Membrane voltage, Na /H exchanger, Na-K-2Cl cotransporter, Secretion",
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Muscarinic activation of Na+-dependent ion transporters and modulation by bicarbonate in rat submandibular gland acinus. / Ji, Eun Lee; Joo, Hyun Nam; Kim, Sungjoon.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 288, No. 4 51-4, 01.04.2005.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Muscarinic activation of Na+-dependent ion transporters and modulation by bicarbonate in rat submandibular gland acinus

AU - Ji, Eun Lee

AU - Joo, Hyun Nam

AU - Kim, Sungjoon

PY - 2005/4/1

Y1 - 2005/4/1

N2 - To investigate the interaction between the ion channels and transporters in the salivary fluid secretion, we measured the membrane voltage (Vm) and intracellular concentrations of Ca2+, Na+ ([Na +]c), Cl-, and H+ (pHi) in rat submandibular gland acini (RSMGA). After a transient depolarization induced by a short application of acetylcholine (ACh; 5 μM, 20 s), RSMGA showed strong delayed hyperpolarization (Vh,ACh; -95 ± 1.8 mV) that was abolished by ouabain. In the HCO3--free condition, the Vh,ACh was also blocked by bumetanide, a blocker of Na+-K+-2Cl- cotransporter (NKCC). In the presence of HCO3- (24 meq, bubbled with 5% CO 2), however, the Vh,ACh was not blocked by bumetanide, but it was suppressed by ethylisopropylamiloride (EIPA), a Na+/H + exchanger (NHE) inhibitor. Similarly, the ACh-induced increase in [Na+]c was totally blocked by bumetanide in the absence of HCO3-, but only by one-half in the presence of HCO 3-. ACh induced a prominent acidification of pH i in the presence of HCO3-, and the acidification was further increased by EIPA treatment. Without HCO 3-, an application of ACh strongly accelerated the NKCC activity that was measured from the decay of pHi during the application of NH4+ (20 mM). Notably, the ACh-induced activation of NKCC was largely suppressed in the presence of HCO 3-. In summary, the ACh-induced anion secretion in RSMGA is followed by the activation of NKCC and NHE, resulting an increase in [Na +]c. The intracellular Na+-induced activation of electrogenic Na+/K+-ATPase causes Vh,ACh. The regulation of NKCC and NHE by ACh is strongly affected by the physiological level of HCO3-.

AB - To investigate the interaction between the ion channels and transporters in the salivary fluid secretion, we measured the membrane voltage (Vm) and intracellular concentrations of Ca2+, Na+ ([Na +]c), Cl-, and H+ (pHi) in rat submandibular gland acini (RSMGA). After a transient depolarization induced by a short application of acetylcholine (ACh; 5 μM, 20 s), RSMGA showed strong delayed hyperpolarization (Vh,ACh; -95 ± 1.8 mV) that was abolished by ouabain. In the HCO3--free condition, the Vh,ACh was also blocked by bumetanide, a blocker of Na+-K+-2Cl- cotransporter (NKCC). In the presence of HCO3- (24 meq, bubbled with 5% CO 2), however, the Vh,ACh was not blocked by bumetanide, but it was suppressed by ethylisopropylamiloride (EIPA), a Na+/H + exchanger (NHE) inhibitor. Similarly, the ACh-induced increase in [Na+]c was totally blocked by bumetanide in the absence of HCO3-, but only by one-half in the presence of HCO 3-. ACh induced a prominent acidification of pH i in the presence of HCO3-, and the acidification was further increased by EIPA treatment. Without HCO 3-, an application of ACh strongly accelerated the NKCC activity that was measured from the decay of pHi during the application of NH4+ (20 mM). Notably, the ACh-induced activation of NKCC was largely suppressed in the presence of HCO 3-. In summary, the ACh-induced anion secretion in RSMGA is followed by the activation of NKCC and NHE, resulting an increase in [Na +]c. The intracellular Na+-induced activation of electrogenic Na+/K+-ATPase causes Vh,ACh. The regulation of NKCC and NHE by ACh is strongly affected by the physiological level of HCO3-.

KW - Acetylcholine

KW - Membrane voltage

KW - Na /H exchanger

KW - Na-K-2Cl cotransporter

KW - Secretion

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U2 - 10.1152/ajpgi.00406.2004

DO - 10.1152/ajpgi.00406.2004

M3 - Article

VL - 288

JO - American Journal of Physiology - Gastrointestinal and Liver Physiology

JF - American Journal of Physiology - Gastrointestinal and Liver Physiology

SN - 0193-1857

IS - 4 51-4

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