Effect of modulating voltage-dependent calcium channels on cholecystokinin and acetylcholine-induced contractions of the guinea pig gallbladder

Parkman, Henry P.; Pagano, Anthony P.; Ringold, Michael A.; Ryan, James P.

doi:10.1016/0167-0115(96)00023-7

Cited by 25 publications

(19 citation statements)

References 29 publications

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“…This mechanism is unlikely to be involved in the GBSM response to CCK, because transient BK currents are RyR mediated and CCK-induced gallbladder contraction is mediated in part by Ca 2ϩ influx through L-type Ca 2ϩ channels (1,1,34,38). Moreover, in our study, suppression of Ca 2ϩ influx by nifedipine caused a reduction in BK currents, indicating a significant role for Ca 2ϩ influx in spark activity and BK currents, whereas in the colon no effects were reported (3) for nicardipine when tested under control conditions or during ACh stimulation.…”

Section: Discussionmentioning

confidence: 99%

“…In the gallbladder, CCKinduced contraction involves the release of Ca 2ϩ from intracellular stores as well as Ca 2ϩ influx through L-type Ca 2ϩ channels (1,34,38). Because the mechanisms responsible for Ca 2ϩ influx in GBSM have not yet been explored and increased protein kinase C activity suppresses BK currents in vascular smooth muscle (8), we tested whether CCK altered transient BK currents in GBSM.…”

Section: Identification Of Camentioning

confidence: 99%

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Ca²⁺sparks and BK currents in gallbladder myocytes: role in CCK-induced response

Pozo

Pérez²,

Nelson³

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

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Pozo, María J., Guillermo J. Pé rez, Mark T. Nelson, and Gary M. Mawe. Ca 2ϩ sparks and BK currents in gallbladder myocytes: role in CCK-induced response. Am J Physiol Gastrointest Liver Physiol 282: G165-G174, 2002. First published October 24, 2001 10.1152/ajpgi.00326. 2002We sought to elucidate the regulation of gallbladder smooth muscle (GBSM) excitability by localized Ca 2ϩ release events (sparks) and large-conductance Ca 2ϩ -dependent (BK) channels by determining whether sparks exist in GBSM and, if so, whether they activate BK channels. Sparks were identified in isolated GBSM loaded with fluo 4. Each spark was associated with a transient outward current, suggesting communication of ryanodine receptor (RyR) channels with BK channels. This was confirmed by the inhibition of outward currents with iberiotoxin (100 nM), thapsigargin (200 nM), and ryanodine (10 M). In current clamp mode, the transient BK currents were associated with brief membrane hyperpolarizations (10.9 Ϯ 1.3 mV). Because transient BK currents could dampen GBSM excitability, we tested whether CCK attenuates these events. CCK (10 nM) reduced the amplitude and frequency of transient BK currents, and subsequent caffeine application restored transient BK current activity. These results support the concept that RyRs and BK channels contribute to the regulation of GBSM excitability and that CCK can act in part by inhibiting this pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Identification Of Camentioning

confidence: 99%

Ca²⁺sparks and BK currents in gallbladder myocytes: role in CCK-induced response

Pozo

Pérez²,

Nelson³

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…For this, high-potassium Krebs solution replaced the normal Krebs solution surrounding the muscle ring in the in vitro muscle bath. The potassium-containing Krebs solutions were prepared by increasing the potassium concentration to 80 mM while decreasing the sodium concentration to maintain osmolality (26).…”

Section: Methodsmentioning

confidence: 99%

Regional gastric contractility alterations in a diabetic gastroparesis mouse model: effects of cholinergic and serotoninergic stimulation

James¹,

Ryan²,

Crowell³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Regional gastric contractility alterations in a diabetic gastroparesis mouse model: effects of cholinergic and serotoninergic stimulation. Am J Physiol Gastrointest Liver Physiol 287: G612-G619, 2004. First published April 23, 2004 10.1152/ ajpgi.00431.2003.-The C57BLKS/J db/db mouse develops hyperglycemia and has delayed gastric emptying that is improved with tegaserod, a partial 5-HT4 agonist. Our aims here were to determine regional gastric contractility alterations in C57BLKS/J db/db mice and to determine the effects of serotonin and tegaserod. The contractile effects of bethanechol, serotonin, and tegaserod in fundic, antral, and pyloric circular muscle were compared in C57BLKS/J db/db mice and normal littermates. The effects of tetrodotoxin, atropine, and 5-HT receptor antagonists were studied. Contractions in response to bethanechol were decreased in the fundus, similar in the antrum, but increased in the pylorus in diabetic mice compared with controls. Serotonin and, to a lesser extent, tegaserod caused contractions that were more pronounced in the fundus than in the antrum and pylorus in both diabetic and normal mice. Serotonin-induced contractions were partially inhibited by atropine, the 5-HT4 antagonist GR113808, and the 5-HT2 antagonist cinanseron but not tetrodotoxin. Regional gastric contractility alterations are present in this diabetic gastroparesis mouse model. Fundic contractility was decreased, but pyloric contractility was increased in the pylorus to cholinergic stimulation in diabetic mice. Serotonin's contractile effect is mediated, in part, through muscarinic, 5-HT2, and 5-HT4 receptors. This study suggests that fundic hypomotility and pyloric hypercontractility, rather than antral hypomotility, play important roles for the gastric dysmotility that occurs in diabetes.serotonin; tegaserod GASTROPARESIS (delayed gastric emptying) is frequent in diabetic patients. It is a well-recognized complication of longstanding diabetes. Although classically, gastroparesis occurs in insulin-dependent diabetic patients, it also develops in type 2 (T2DM) or non-insulin-dependent diabetes mellitus (15). Gastroparesis is associated with antral hypomotility and perhaps pyloric dysfunction (2, 23).Treatment of gastroparesis is with prokinetic agents, which accelerate gastric emptying. Tegaserod, an aminoguanidine indole compound, is a recently developed 5-HT 4 partial agonist (1). Activation of 5-HT 4 receptors triggers the release of neurotransmitters from the enteric nerves resulting in increased contractility and stimulation of the peristaltic reflex (10). Tegaserod has been shown to accelerate gastric emptying in some (6) but not all studies (28).Strains of rats and mice with spontaneously developing hyperglycemia have been recognized as useful models to study the effects of diabetes. The Jackson Laboratory C57BLKS/J db/db mouse spontaneously develops hyperglycemia (12) and is a model for non-insulin-dependent diabetes mellitus (24). Prior studies in this mouse strain (22) have shown delayed gastric em...

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“…The concept of capacitative entry involves only operation of non-voltage-operated channels. However, L-type Ca 2ϩ channels play a dominant role in this cell type, in response to stimulation and in resting conditions (2,3,26). Therefore, we evaluated whether L-type Ca 2ϩ channels are somehow activated by the emptying of the stores.…”

Section: Cce Is Present In Gbsm Cells Tps Is a Specific Inhibitor Ofmentioning

confidence: 99%

“…In gallbladder smooth muscle (GBSM), CCE has not been reported, although Ca 2ϩ influx is determinant in the contractile responses: we previously showed that L-type Ca 2ϩ channels are important in the maintenance of gallbladder resting tone (3), similar to the well-known role of extracellular Ca 2ϩ in the contractile response to agonists (2,3,26,32). In addition, we also found that, in GBSM cells, localized Ca 2ϩ release from SR regulates plasma membrane potential by activation of Ca 2ϩ -activated K ϩ channels (27).…”

mentioning

confidence: 99%

Coactivation of capacitative calcium entry and L-type calcium channels in guinea pig gallbladder

Morales

Camello²,

Alcon³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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We have evaluated the presence of capacitative Ca2+ entry (CCE) in guinea pig gallbladder smooth muscle (GBSM), including a possible relation with activation of L-type Ca2+ channels. Changes in cytosolic Ca2+ concentration induced by Ca2+ entry were assessed by digital microfluorometry in isolated, fura 2-loaded GBSM cells. Application of thapsigargin, a specific inhibitor of the Ca2+ store pump, induced a transient Ca2+ release followed by sustained entry of extracellular Ca2+. Depletion of the stores with thapsigargin, cyclopiazonic acid, ryanodine and caffeine, high levels of the Ca2+-mobilizing hormone cholecystokinin octapeptide, or simple removal of external Ca2+ resulted in a sustained increase in Ca2+ entry on subsequent reapplication of Ca2+. This entry was attenuated by 2-aminoethoxydiphenylborane, L-type Ca2+ channel blockade, pinacidil, and Gd3+. Accumulation of the voltage-sensitive dye 3,3′-dipentylcarbocyanine and direct intracellular recordings showed that depletion of the stores is sufficient for depolarization of the plasma membrane. Contractility studies in intact gallbladder muscle strips showed that CCE induced contractions. The CCE-evoked contraction was sensitive to 2-aminoethoxydiphenylborane, L-type Ca2+ channel blockers, and Gd3+. We conclude that, in GBSM, release of Ca2+ from internal stores activates a CCE pathway and depolarizes plasma membrane, allowing coactivation of voltage-operated L-type Ca2+ channels. This process may play a role in excitation-contraction coupling in GBSM.

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Effect of modulating voltage-dependent calcium channels on cholecystokinin and acetylcholine-induced contractions of the guinea pig gallbladder

Cited by 25 publications

References 29 publications

Ca²⁺sparks and BK currents in gallbladder myocytes: role in CCK-induced response

Ca²⁺sparks and BK currents in gallbladder myocytes: role in CCK-induced response

Regional gastric contractility alterations in a diabetic gastroparesis mouse model: effects of cholinergic and serotoninergic stimulation

Coactivation of capacitative calcium entry and L-type calcium channels in guinea pig gallbladder

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Effect of modulating voltage-dependent calcium channels on cholecystokinin and acetylcholine-induced contractions of the guinea pig gallbladder

Cited by 25 publications

References 29 publications

Ca2+sparks and BK currents in gallbladder myocytes: role in CCK-induced response

Ca2+sparks and BK currents in gallbladder myocytes: role in CCK-induced response

Regional gastric contractility alterations in a diabetic gastroparesis mouse model: effects of cholinergic and serotoninergic stimulation

Coactivation of capacitative calcium entry and L-type calcium channels in guinea pig gallbladder

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Ca²⁺sparks and BK currents in gallbladder myocytes: role in CCK-induced response

Ca²⁺sparks and BK currents in gallbladder myocytes: role in CCK-induced response