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S Muallem

Publications and source records attributed to S Muallem.

At least 109 records · Page 6Linked to original sources
PubMed1989

Modulation of osteoblast function by prostaglandins.

The naturally occurring prostaglandins (PGs) were studied with respect to their abilities to change free cytosolic Ca2+ concentrations ([Ca2+]i), adenosine 3',5'-cyclic monophosphate (cAMP) levels, and cell proliferation in the osteoblastic cell line, UMR-106-01, and primary cultures of osteoblasts prepared from neonatal rat calvariae. All PGs tested stimulated an increase in [Ca2+]i, which was mainly due to Ca2+ release from intracellular stores. Measurements of the 50% effective concentration for the different PGs show that the potency ranking for PG-evoked [Ca2+]i increase in these cells is F2 alpha greater than D2 much greater than E2 greater than TxB2 greater than E1 greater than I2 much greater than A2. The PGs also increase cAMP levels in osteoblasts. At the highest concentrations tested (10-25 microM), dose-response saturation of cAMP production was observed only by PGE2 and PGE1. The potency rank for PG-stimulated cAMP increase was E2 greater than E1 much greater than A2 greater than I2 greater than F2 alpha greater than D2 greater than TxB2. Measurements of the effect of the PGs on thymidine uptake showed that low concentrations of PGF2 alpha and PGD2 had either no effect or stimulated proliferation of osteoblast-like cells. Relatively low concentration of PGE2, PGE1, and PGA2 inhibited proliferation. The potency ranking for PG-mediated inhibition of cell proliferation was identical to that found for PG-stimulated cAMP production. We conclude that all the naturally occurring PGs tested can activate the two signal transduction systems in osteoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗
PubMed1988

Activation of the Na+/H+ and Cl-/HCO3- exchange by stimulation of acid secretion in the parietal cell.

Upon stimulation, the gastric parietal cell secretes a large quantity of isotonic HCl across its apical membrane which must be accompanied by the generation of base in the cytosol. The ability of this cell type to regulate cytosolic pH (pHi) was examined as a function of stimulation of acid secretion by histamine or forskolin. The pHi was estimated from the change of fluorescence of the trapped dye, 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein-bis-carboxyethylcarbo xy fluorescein in a purified cell suspension of rabbit parietal cells. Stimulation of the cell suspension raised pHi by an average of 0.13 +/- 0.038 pH units. The H+,K+-ATPase inhibitor, SCH28080 (2-methyl-8-[phenyl-methoxy]-imidazo-(1,2)-pyridine-3-acetonitrile) had only a small effect on the increase of pHi, therefore, was largely independent of H+,K+-ATPase activity. In Na+-free medium, where Na+/H+ exchange would be absent, the rise of pHi was only 0.03 pH units. This increase was blocked by SCH28080, showing that this small increment was the result of acid secretion. In Na+-containing medium, 90% of the increase was inhibited by an inhibitor of Na+/H+ exchange, dimethyl amiloride (DMA). This compound also blocked changes in pHi due to changes in extracellular Na+. Accordingly, most of the change in pHi upon stimulation of acid secretion by histamine and forskolin is due to activation of Na+/H+ exchange in the parietal cell basal-lateral membrane. The addition of DMA to stimulated, but not resting cells, gave a rapid acidification that was blocked by inhibition of anion exchange by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), showing that anion exchange was also activated by stimulation. In single cell recording, canalicular and cytosolic pH were monitored simultaneously using 9-amino acridine and dimethyl carboxyfluorescein, respectively. Cytosolic alkalinization correlated with acid accumulation in the secretory canaliculus until a set point was reached. Thereafter, acidification continued without further change in pHi. To determine the role of Na+/H+ and Cl-/HCO3- exchange in acid secretion, Cl(-)-depleted cells were suspended in medium containing 40 mM Cl-. DMA and DIDS each blocked acid secretion by about 40%, but in combination, acid secretion was blocked by more than 90%. Thus, basal-lateral Na+/H+ and Cl-/HCO3- exchange activities are necessary for acid secretion across the apical membrane of the parietal cell.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1988

Two components of hormone-evoked calcium release from intracellular stores of pancreatic acinar cells.

Dispersed pancreatic acini loaded with Fura 2 were used to study the effect of hormonal stimulation on [Ca2+]i (free cytosolic Ca2+ concentration). Stimulation of acini with cholecystokinin octapeptide or carbachol resulted in two components of increase in [Ca2+]i. The maximal increase in [Ca2+]i and the time to maximum for both components was dependent on hormone concentration. The first component reached a maximum after 2-10 s of stimulation, whereas the second component required 30-60 s of stimulation for maximal effect. Both components of the [Ca2+]i increase can be observed in the presence or absence of Ca2+ in the incubation medium. The two components of Ca2+ release from intracellular stores showed similar dependency on agonist concentration. Termination of cell stimulation with specific antagonist revealed two, kinetically separated, rates of decrease in [Ca2+]i. The initial decrease in [Ca2+]i, was completed within 2.5-7 s, whereas the secondary decrease in [Ca2+]i, back to resting values, required approx. 40 s. The magnitude of the antagonist-induced initial (rapid) and secondary (slow) decrease in [Ca2+]i was dependent on the duration of cell stimulation. Hence it appears that stimulation of pancreatic acinar cells with Ca2+-mobilizing hormones results in two, kinetically separated, components of Ca2+ release from intracellular stores.

Animals↗
PubMed1988

Relationship of cAMP and calcium messenger systems in prostaglandin-stimulated UMR-106 cells.

The effect of prostaglandins (PG) on free cytosolic calcium concentrations [( Ca2+]i) and cAMP levels was studied in the osteosarcoma cell line UMR-106. PGF2 alpha and PGE2, but not 6-keto-PGF1 alpha, induced an increase in [Ca2+]i which was mainly due to Ca2+ release from intracellular stores. The EC50 for PGF2 alpha was approximately 7 nM, whereas that for PGE2 was approximately 1.8 microM. Maximal doses of PGF2 alpha increased [Ca2+]i to higher levels than PGE2. Both active PGs also stimulated phosphatidylinositol turnover in UMR-106 cells. The effects of the two PGs were independent of each other and appear to involve separate receptors for each PG. PGE2 was a very potent stimulator of cAMP production and increased cAMP by approximately 80-fold with an EC50 of 0.073 microM. PGF2 alpha was a very poor stimulator of cAMP production; 25 microM PGF2 alpha increased cAMP by 5-fold. The increase in cellular cAMP levels activated a plasma membrane Ca2+ channel which resulted in a secondary, slow increase in [Ca2+]i. High concentrations of both PGs (10-50 microM) inhibited this channel independent of their effect on cAMP levels. Pretreatment of the cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate inhibited the PG-mediated increase in phosphatidylinositol turnover and the increase in [Ca2+]i. However, pretreatment with 12-O-tetradecanoyl-13-acetate had no effect on the PGE2-mediated increase in cAMP. The latter finding, together with the dose responses for PGE2-mediated increases in [Ca2+]i and cAMP levels, suggests the presence of two subclasses of PGE2 receptors: one coupled to adenylate cyclase and the other to phospholipase C. With respect to osteoblast function, the cAMP signaling system is antiproliferative, whereas the Ca2+ messenger system, although having no proliferative effect by itself, tempers cAMP's antiproliferative effect.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Selective modification of the kinetic properties of Na+/H+ exchanger by cell shrinkage and swelling.

The effect of volume perturbation on the interaction of Na+ and H+ with the intracellular and extracellular faces of the Na+/H+ exchanger was studied in UMR-106 cells, a rat osteosarcoma cell line. Osmotic shrinkage of the cells stimulated the activity of the Na+/H+ exchanger. Kinetic analysis of this stimulation demonstrated that in hyperosmotically stressed cells, the apparent affinities for intracellular H+ and intracellular Na+ are modified in opposite directions. While there is an increased apparent affinity for protons from 0.275 +/- 0.03 to 0.107 +/- 0.025 microM in isotonic and hypertonic conditions, respectively, the apparent affinity for intracellular Na+ decreases from 83 +/- 9 to 126 +/- 6 mM under the same conditions. Osmotic swelling induced a decreased exchanger activity which appeared to involve reduction in Vmax only without changes in the apparent affinities of either H+i or Na+i. We conclude that: 1) osmotic shrinkage and swelling modify the kinetic behavior of the Na+/H+ exchanger in different modes; 2) in hyperosmotically stressed cells, the interactions of intracellular H+ and Na+ are modified in a selective mode. The described phenomenon may serve as a general mechanism for activation of the exchanger by various stimuli.

Animals↗
PubMed1988

Role of Na+/Ca2+ exchange and the plasma membrane Ca2+ pump in hormone-mediated Ca2+ efflux from pancreatic acini.

The relative contributions of the Na+/Ca2+ exchange and the plasma membrane Ca2+ pump to active Ca2+ efflux from stimulated rat pancreatic acini were studied. Na+ gradients across the plasma membrane were manipulated by loading the cells with Na+ or suspending the cells in Na+-free media. The rates of Ca2+ efflux were estimated from measurements of [Ca2+]i using the Ca2+-sensitive fluorescent dye Fura 2 and 45Ca efflux. During the first 3 min of cell stimulation, the pattern of Ca2+ efflux is described by a single exponential function under control, Na+-loaded, and Na+-depleted conditions. Manipulation of Na+ gradients across the plasma membrane had minimal effects on resting [Ca2+]i, the rate constant of Ca2+ efflux, and [Ca2+]i levels attained by the cells after 5 min of stimulation. Changing Na+ gradients had no effect on the hormone-induced increase in [Ca2+]i. The results indicate that Ca2+ efflux from stimulated pancreatic acinar cells is mediated by the plasma membrane Ca2+ pump. The effects of several cations, which were used to substitute for Na+, on cellular activity were also studied. Choline+ and tetramethylammonium+ (TMA+) released Ca2+ from intracellular stores of pancreatic acinar, gastric parietal and peptic cells. These cations also stimulated enzyme and acid secretion from the cells. All effects of these cations were blocked by atropine. Measurements of cholecystokinin-octapeptide (CCK-OP)-stimulated amylase release from pancreatic acini, suspended in Na+, TMA+, choline+, or N-methyl-D-glucamine+ (NMG+) media containing atropine, were used to evaluate the effect of the cations on cellular function. NMG+, choline+, and TMA+ inhibited amylase release by 55, 40 and 14%, respectively. NMG+ also increased the Ca2+ permeability of the plasma membrane. Thus, to study Na+ dependency of cellular function, TMA+ is the preferred cation to substitute for Na+. The stimulatory effect of TMA+ can be blocked by atropine.

Animals↗
PubMed1988

Calcium mobilizing hormones activate the plasma membrane Ca2+ pump of pancreatic acinar cells.

45Ca fluxes and free-cytosolic Ca2+([Ca2+]i) measurements were used to study the effect of Ca2+-mobilizing hormones on plasma membrane Ca2+ permeability and the plasma membrane Ca2+ pump of pancreatic acinar cells. We showed before (Pandol, S.J., et al., 1987. J. Biol. Chem. 262:16963-16968) that hormone stimulation of pancreatic acinar cells activated a plasma membrane Ca2+ entry pathway, which remains activated for as long as the intracellular stores are not loaded with Ca2+. In the present study, we show that activation of this pathway increases the plasma membrane Ca2+ permeability by approximately sevenfold. Despite that, the cells reduce [Ca2+]i back to near resting levels. To compensate for the increased plasma membrane Ca2+ permeability, a plasma membrane Ca2+ efflux mechanism is also activated by the hormones. This mechanism is likely to be the plasma membrane Ca2+ pump. Activation of the plasma membrane Ca2+ pump by the hormones is time dependent and 1.5-2 min of cell stimulation are required for maximal Ca2+ pump activation. From the effect of protein kinase inhibitors on hormone-mediated activation of the pump and the effect of the phorbol ester 12-0-tetradecanoyl phorbol, 13-acetate (TPA) on plasma membrane Ca2+ efflux, it is suggested that stimulation of protein kinase C is required for the hormone-dependent activation of the plasma membrane Ca2+ pump.

Animals↗
PubMed1988

Passive and active transport in the parietal cell.

1. Models are presented for (a) HK ATPase acting in the presence of K and Cl conductances; (b) a pH regulatory system where Na/H exchange is regulated directly by second messenger and the anion exchanger is activated secondarily to the rise in cell pH; (c) vesicle fusion and K and Cl conductances activation in the gastric parietal cell. 2. It is suggested that H transport involves protonation and deprotonation of histidine groups as well as the motion of these groups relative to the membrane barrier. 3. The HK ATPase would have a voltage generating and voltage sensitive step in the forward direction. 4. Given net electroneutrality the K transport reaction would also be charge translocating and voltage sensitive.

Animals↗
PubMed1988

Cytosolic pH regulation in osteoblasts. Interaction of Na+ and H+ with the extracellular and intracellular faces of the Na+/H+ exchanger.

The interaction of Na and H ions with the extracellular and intracellular sites of the Na+/H+ exchanger of the osteosarcoma cell line UMR-106 was investigated. Na ions interact with a single, saturable extracellular transport site. H+ and amiloride appear to compete with Na+ for binding to this site. The apparent affinity for extracellular Na+ (Nao+) and amiloride was independent of intracellular H+ (Hi+), Nai+, or an outwardly directed H+ gradient. The interaction of H+ with the intracellular face of the exchanger had a sigmoidal characteristic with a Hill coefficient of approximately 2. The apparent affinity for Hi+ was independent of Nao+ between 25 and 140 mM. The apparent affinity for Hi+, but not the number of intracellular sites, increased with the increase in the outwardly directed H+ gradient across the membrane. Nai+/Ho+ exchange (reverse mode) is an electroneutral process with a Na+/H+ stoichiometry of 1. The dependence of Nai+/Ho+ exchange on Nai+ was sigmoidal, with a Hill coefficient of 2.16. Nai+ competes with Hi+ for binding to at least the transport site. The apparent affinity for Nai+ decreased with the increase in the outwardly directed H+ gradient. High Ho+ inhibited exchange activity in the reverse mode. We conclude that intracellular Na+ and H+ can activate the exchanger. The exchanger has two separate and asymmetric extracellular and intracellular transport sites. The relative apparent affinities of the internal transport site for Na+ and H+ are determined by the direction and magnitude of the H+ gradient across the membrane. Kinetic characterization of the exchanger suggests that Na+/H+ exchange is compatible with a simultaneous transport model, although a ping-pong transport model could not be excluded.

Amiloride↗
PubMed1988

Agonist-sensitive calcium pool in the pancreatic acinar cell. I. Permeability properties.

45Ca2+ fluxes and free cytosolic Ca2+ [( Ca2+]i) were used to describe the Ca2+ permeability and Ca2+ reloading of the agonist-sensitive pool at rest, during stimulation, and at termination of stimulation. A sequence of stimulation with carbachol, inhibition with atropine (cycling), and restimulation with cholecystokinin octapeptide (CCK-8) was used to follow Ca2+ reloading. Reloading of the pool required extracellular Ca2+ and was measured as an increased rate and extent of 45Ca2+ uptake into the acini. The 45Ca2+ incorporated into cycled acini could be completely released with CCK-8. The dose-response curves for 45Ca uptake and release were identical to those of the hormonally evoked [Ca2+]i increase. The increased 45Ca2+ uptake during reloading was not due to an expansion of any intracellular pool size but reflects the labeling of the pool to isotopic equilibrium in cycled acini. The rate constant of Ca2+ efflux from the pool of resting cells was approximately 0.67 +/- 0.01/h. With stimulation, the Ca2+ permeability of the pool membrane rapidly increased, resulting in Ca2+ release into the cytosol and an increase in [Ca2+]i. With termination of stimulation, the Ca2+ permeability of the pool membrane rapidly decreased while the pool continued to reload with extracellular Ca2+. Labeling of the pool to isotopic equilibrium allowed determination of the amount of Ca2+ released from the pool, which was 2.94 +/- 0.06 nmol/mg protein. This indicates that total Ca2+ concentration in the pool is in the millimolar range.

Animals↗
PubMed1988

Agonist-sensitive calcium pool in the pancreatic acinar cell. II. Characterization of reloading.

45Ca2+ fluxes and free cytosolic Ca2+ measurements in guinea pig pancreatic acini indicated that after agonist stimulation and the release of Ca2+ from the agonist-sensitive pool at least part of the Ca2+ is extruded from the cell, resulting in 45Ca2+ efflux. In the continued presence of agonist, the pool remains permeable to Ca2+ but partially refills with Ca2+. This reloading is dependent on the concentration of extracellular Ca2+. In the absence of extracellular Ca2+, the pool is completely depleted of Ca2+. However, with increasing concentrations of CaCl2 in the incubation solution (from 0.5 to 2.0 mM) there is increasing repletion of the pool with Ca2+ during agonist stimulation. With termination of agonist stimulation, the Ca2+ permeability of the agonist-sensitive pool is rapidly reduced to that measured in the unstimulated cell. As a result, the Ca2+ incorporated into the pool during the stimulation period is rapidly trapped within the pool and exchanges poorly with medium Ca2+. Subsequently, the pool completely refills with Ca2+. The rate of Ca2+ reloading at the termination of agonist stimulation is slower than the conversion of the pool to the impermeable state. In incubation media containing 1.3 mM CaCl2, the half-time for reloading at the termination of stimulation is 5 min. These observations demonstrate the characteristics of Ca2+ reloading of the agonist-sensitive pool both during stimulation and at the termination of stimulation.

Animals↗
PubMed1988

Modulation of Na+-H+ exchange activity by intracellular Na+, H+, and Li+ in IMCD cells.

In the present study, cultured inner medullary collecting duct (IMCD) cells loaded with the pH-sensitive dye 2',7' bis(carboxyethyl)-carboxyfluorescein were used to study the interaction of H+, Na+, and Li+ with the intracellular face of the Na+-H+ exchanger. The interaction of Na+ with the external face of the exchanger followed simple saturation kinetics with an apparent affinity for Na+ of 19.5 +/- 2 mM (n = 3) at an extracellular pH of 7.4. Extracellular H+ and Li+ inhibit Na+o-H+i exchange, mainly due to interference with Na+ binding to an external site or the same enzyme intermediate species in the turnover cycle of the Na+-H+ exchanger. The interaction of H+ with the internal face of the exchanger does not follow simple saturation kinetics. The calculated Hill coefficient for H+ interaction with intracellular sites was 1.92. Na+ and Li+ also interact with the intracellular face of the Na+-H+ exchanger. This interaction of Li+ and Na+ with internal sites results in inhibition of Na+-H+ exchange activity in the forward direction (Na+ influx/H+ efflux). The inhibitory effect of intracellular Na+ and Li+ is pHi dependent and most apparent under physiological conditions, i.e., at an intracellular pH of 7.1, an extracellular pH of 7.4, and an extracellular Na+ of 140 mM. This study shows the importance of intracellular Na+ concentration in determining exchanger activity.

Amiloride↗
PubMed1987

The agonist-sensitive calcium pool in the pancreatic acinar cell. Activation of plasma membrane Ca2+ influx mechanism.

The purposes of the present study were to investigate the characteristics and regulation of Ca2+ influx across the plasma membrane in pancreatic acini and to demonstrate the role of this Ca2+ influx in the mechanism of reloading of the agonist-sensitive Ca2+ pool. In pancreatic acini, depleted of intracellular Ca2+ by stimulation with carbachol in the absence of extracellular Ca2+, 25 microM LaCl3 inhibited the increase in free cytosolic Ca2+ ([Ca2+]i) and reloading of the agonist-sensitive pool that occurred with the addition of extracellular CaCl2 to the medium. LaCl3 also inhibited the increase in cellular 45Ca2+ uptake that occurred during agonist stimulation and its termination but not cellular 45Ca2+ uptake into unstimulated acini. In acini depleted of intracellular Ca2+, increased cellular Ca2+ influx and reloading of the agonist-sensitive pool occurred even if extracellular CaCl2 was added 10 min after the termination of agonist action. Maximal reloading was independent of the extracellular Ca2+ concentration between 0.5 and 2.0 mM CaCl2. However, the time to maximal reloading was longer at lower extracellular Ca2+ concentrations. These results demonstrate a plasma membrane Ca2+ influx mechanism in the pancreatic acinar cell that is activated during cell stimulation. This transport remains activated as long as the agonist-sensitive pool is not completely loaded with Ca2+ suggesting that the Ca2+ influx mechanism is regulated by the quantity of Ca2+ in the agonist-sensitive pool. The activation of this Ca2+ transport mechanism functions to allow Ca2+ influx across the plasma membrane and Ca2+ reloading of the agonist-sensitive pool. Furthermore, these results suggest that during reloading Ca2+ crosses the plasma membrane into the cytosol before entering the agonist-sensitive pool.

Animals↗
PubMed1987

Activation of the endoplasmic reticulum Ca2+ pump of pancreatic acini by Ca2+ mobilizing hormones.

Stimulation of the pancreatic acinar cells with Ca2+ mobilizing hormones increased the ATP-dependent Ca2+ uptake into the ER of permeabilized cells. Activation of the ER Ca2+ pump resulted in increased apparent affinity for Ca2+ from 0.26 to 0.09 uM and Vmax from 2.68 to 5.74 nmoles/mg prot./min. The apparent affinity of the pump for VO4 = was dependent on [Ca2+]. Activation of the pump also decreased apparent affinity for VO4 = from 12 to 32 uM at [Ca2+] of 0.138 uM. These findings suggest that pump activation is due to acceleration of the rate of the conformational transition between the VO4 = (E2) and Ca2+ (E1) sensitive forms of the pump.

Adenosine Triphosphate↗
PubMed1987

Protein kinase C-activated calcium channel in the osteoblast-like clonal osteosarcoma cell line UMR-106.

The effects of protein kinase C stimulation on free cytosolic Ca2+ [( Ca2+]i) were studied in Fura 2-loaded UMR-106 cells. Stimulation of the protein kinase C with the tumor-promoting phorbol esters 12-O-tetradecanoylphorbol 13-acetate (TPA) and phorbol 12,13-diacetate or 1-oleoyl-2-acetylglycerol was followed by an increase in [Ca2+]i. The protein kinase C-induced increase in [Ca2+]i has a lag period, the duration of which was dependent on the stimulant and medium Ca2+ concentrations. With 2 microM TPA, the rise in [Ca2+]i peaked within 1.5 min, after which [Ca2+]i returned partially toward base line. The increase in [Ca2+]i was absolutely dependent on the presence of medium Ca2+ and was inhibited by the Ca2+ channel blockers nicardipine and verapamil. Cell stimulation also results in Ca2+ release from intracellular pool(s) which appears to be mediated by a Ca2+-dependent Ca2+ release mechanism. The reduction in [Ca2+]i was due to channel inactivation. Pretreatment of the cells with 1 nM TPA, 2 units/ml parathyroid hormone (PTH), or 15 microM forskolin blocked the effect of 2 microM TPA on [Ca2+]i. TPA and PTH were more potent inhibitors than was forskolin. The properties of this channel are compared to the cAMP-independent PTH-stimulated Ca2+ channel present in these cells.

Calcium↗
PubMed1987

Parathyroid hormone-activated calcium channels in an osteoblast-like clonal osteosarcoma cell line. cAMP-dependent and cAMP-independent calcium channels.

Changes in free cytosolic calcium were measured in UMR-106 cells in response to parathyroid hormone (PTH) stimulation. Bovine PTH-(1-34) induced an increase in [Ca2+]i with the contour of the rise in [Ca2+]i occurring in three successive phases: a rapid increase in [Ca2+]i occurring within seconds, rapid decrement in [Ca2+]i to near-resting levels within 1 min, and slow increment in [Ca2+]i. Phase one and phase three increases in [Ca2+]i were dependent on medium calcium. The phase one rise in [Ca2+]i was inhibitable by the calcium channel blockers lanthanum and verapamil. Only the phase one rise in [Ca2+]i was blocked by preincubation of the cells with the phorbol ester, phorbol 12-myristate 13-acetate. This channel was also blocked when cellular cAMP levels were increased prior to PTH stimulation. The phase two decrement of [Ca2+]i was due to the rapid inactivation of the phase one calcium channel. The phase three rise in [Ca2+]i was mediated by cellular cAMP levels. This cAMP-dependent Ca2+ channel was insensitive to pretreatment of the cells with phorbol diesters and showed low sensitivity to Ca2+ channel blockers. It is concluded that UMR-106 cells respond to PTH stimulation by the activation of a cAMP-independent Ca2+ channel. This channel rapidly inactivates. The subsequent PTH-dependent increase in cellular cAMP is followed by activation of a cAMP-dependent Ca2+ channel resulting in a slow rise in [Ca2+]i.

Animals↗