Biomedical subjects

M Oike

Publications and source records attributed to M Oike.

At least 19 recordsLinked to original sources

PubMed1998

Increase in calcium in smooth muscle cells of the rabbit bladder induced by acetylcholine and ATP.

Cultured smooth muscle cells from rabbit urinary bladder were loaded with fura-2. Changes in intracellular Ca concentration [Ca2+]i produced by acetylcholine (ACh) or adenosine triphosphate (ATP) were estimated by measuring the fluorescence ratio F340/F380. Western blot analysis and immunohistochemical techniques showed that the cultured cells retained alpha-smooth muscle actin. ATP produced a rapid but transient increase in [Ca2+]i and ACh produced a delayed, prolonged increase. Application of ACh after ATP in Ca-free solution failed to elevate [Ca2+]i suggesting that both ACh and ATP release Ca2+ from the same intracellular stores. Following application of ACh but not ATP in Ca-free Krebs solution, reintroduction of Ca2+ produced elevation of [Ca2+]i, indicating that ACh causes prolonged opening of channels in the membrane. The sustained increase induced by ACh was abolished by nicardipine (blocker of Ca2+ voltage dependent channel ICa(V)) or quinine (blocker of non-selective cation channels). Although the elevations to ACh or ATP were abolished by neomycin (an inhibitor of phospholipase C) the different time courses suggest that the mechanisms of release of Ca2+ from intracellular stores or the pathway for refilling the stores is different.

Acetylcholine↗

PubMed1998

Acute glucose overload abolishes Ca2+ oscillation in cultured endothelial cells from bovine aorta: a possible role of superoxide anion.

Effects of acute glucose overload on [Ca2+]i were investigated in cultured endothelial cells from bovine aorta. Application of 0.1 micromol/L ATP elicited an oscillatory increase in [Ca2+]i (Ca2+ oscillation) in Krebs solution containing 11.5 mmol/L glucose. The frequency of Ca2+ oscillation induced by ATP increased in a concentration-dependent manner, ranging between 0.03 and 1 micromol/L. When cells were preincubated with 23 mmol/L glucose-containing Krebs solution (high glucose solution) for 3 hours, 0.1 micromol/L ATP failed to induce Ca2+ oscillation but evoked only a phasic followed by sustained increase in [Ca2+]i. Application of a higher concentration of ATP (10 micromol/L) evoked a transient increase in [Ca2+]i both in control and high glucose-treated cells. However, the falling phase of [Ca2+]i was prolonged in high glucose-treated cells. Thapsigargin (1 micromol/L), an inhibitor of endoplasmic Ca2+-ATPase, induced a transient followed by a sustained increase in [Ca2+]i in control cells. Preincubation with high glucose solution increased the rate of rise of the thapsigargin-induced increase in [Ca2+]i and abolished the sustained increase, suggesting that glucose overload accelerates Ca2+ leak from intracellular store sites and impairs Ca2+ release-activated Ca2+ entry. We found that all of the glucose overload-induced changes in Ca2+ mobilization could be mimicked by xanthine with xanthine oxidase and abolished by superoxide dismutase. These results indicate that acute glucose overload accumulates superoxide anion in bovine aortic endothelial cells, thereby diminishing ATP-induced Ca2+ oscillation through the impairment of Ca2+ homeostasis.

Adenosine Triphosphate↗

PubMed1998

Effects of acute glucose overload on histamine H2 receptor-mediated Ca2+ mobilization in bovine cerebral endothelial cells.

[Ca2+]i and whole-cell membrane current were measured in microvascular endothelial cells from bovine brain. The effects of histamine on [Ca2+]i were examined, and the acute effect of changing extracellular glucose concentration on Ca2+ homeostasis was investigated. Application of 10 micromol/l histamine evoked an initially transient and then sustained increase in [Ca2+]i in normal Krebs solution, but only the transient component in Ca2+-free solution, thereby indicating that histamine mobilizes Ca2+ both from intracellular store sites and extracellular space. The effects of histamine on [Ca2+]i were inhibited by the H2 antagonists, ranitidine and cimetidine, but not by the H1 antagonist, pyrilamine. Incubation of the cells for 2 h in solutions containing low (1.1 and 2.3 mmol/l) or high (23 mmol/l) concentrations of glucose did not influence the resting level of [Ca2+]i. Treatment with low concentrations of glucose did not impair histamine-induced Ca2+ mobilization. On the other hand, when histamine was applied to the cells pretreated with 23 mmol/l glucose, it failed to mobilize Ca2+ from both intracellular store sites and extracellular space. The effect of histamine was mimicked by dibutyryl cyclic AMP, but glucose overload failed to inhibit this, suggesting that glucose overload inhibits H2 receptor-mediated cyclic AMP production. Glucose overload-induced impairment of histamine action was reversed by pretreatment with staurosporine and calphostin C and mimicked by phorbol-12,13-dibutyrate, thereby suggesting the involvement of protein kinase C in the high glucose-induced inhibition of Ca2+ mobilization. Whole-cell membrane current measurement showed that there was no difference in the membrane currents between control and high glucose-treated cells. These results indicate that in bovine brain microvascular endothelial cells, histamine induces Ca2+ release from intracellular store sites and subsequent entry from the extracellular space through the activation of H2 receptors. Glucose overload acutely inhibits histamine-induced Ca2+ mobilization by the activation of protein kinase C.

Animals↗

PubMed1997

Dynamic regulation of intracellular Ca2+ concentration in aortic endothelial cells.

In non-excitable cells, a Ca2+ entry pathway is opened after the depletion of intracellular Ca2+ store sites. We have tried to estimate the sensitivity of this pathway to Ca2+ release using bovine aortic endothelial cells. Single application of a high concentration (30 microM) of ATP released almost all stored Ca2+ in Ca(2+)-free extracellular solution, whereas a low concentration of ATP (30 nM) produced a partial (57.3 +/- 3.0%) release of Ca2+. By 10 min of Ca2+ re-perfusion, the Ca2+ store site was reloaded to 97.1% of its initial filling state. When thapsigargin was applied to this cell in Mn2+ solution, Mn(2+)-induced quenching of fura-2 dye started when 19.3 +/- 5.3% of Ca2+ release, produced by 30 nM ATP, had occurred. Therefore, Ca2+ release required for Mn2+ entry was estimated as 11.1 +/- 3.0% of stored Ca2+. These results indicate that intracellular Ca2+ concentration is controlled dynamically by simultaneously occurring Ca2+ release and entry in bovine aortic endothelial cells.

Adenosine Triphosphatases↗

PubMed1997

Membrane tumor necrosis factor-alpha (TNF-alpha) expressed on HTLV-I-infected T cells mediates a costimulatory signal for B cell activation--characterization of membrane TNF-alpha.

The 26-kDa membrane tumor necrosis factor-alpha (TNF-alpha) expressed on activated CD4(+) T cells is a novel candidate for the functional membrane molecule in T-B cell interactions. We found that normal human T cells, when infected with human T cell lymphotropic virus type I (HTLV-I) in vitro, were induced to express the 26-kDa membrane TNF-alpha. The infected T cells, through this molecule, activated autologous B cells to produce immunoglobulin (Ig)M in a contact-dependent manner, which was partially inhibited by anti-TNF-alpha antibody (Ab). IgG synthesis was not stimulated, however, probably because of lack of CD40 ligand expression on the infected T cells. Anti-TNF-alpha Ab treatment stimulated the secretion of interleukin (IL)-2 and interferon gamma (IFN-gamma) in the infected T cells. These effects were not induced by anti-TNF receptor Ab treatment. Anti-TNF-alpha Ab also induced the elevation of intracellular calcium concentration in the infected T cells. These results suggest that T cells expressing membrane TNF-alpha can be directly stimulated through this molecule. Thus, it is suggested that the 26-kDa membrane TNF-alpha on HTLV-I-infected T cells plays a role in polyclonal B cell activation and may be involved in the pathogenesis of some HTLV-I-associated diseases. Additionally, our results suggest a novel mechanism by which cytokine production can be modulated in these T cells through membrane TNF-alpha on their surface.

Antigen Presentation↗

PubMed1997

Hydrogen peroxide induced responses of cat tracheal smooth muscle cells.

1. The effects of hydrogen peroxide (H2O2) (10(-6)-10(-3) M) on membrane potential, membrane currents, intracellular calcium concentration, resting muscle tone and contractions elicited by electrical field stimulation (EFS) and carbachol were examined in cat tracheal strips and isolated smooth muscle cells. 2. H2O2 (10(-4) and 10(-5) M) enhanced the amplitude of contractions and excitatory junction potentials (e.j.p.) evoked by EFS without changing muscle tone and resting membrane potential of the tracheal smooth muscle, and enhanced the contraction induced by carbachol (10(-3) M). At an increased concentration (10(-3) M), H2O2 elevated resting muscle tone and marginally hyperpolarized the membrane in the majority of the cells. 3. In 51 out of 56 cells examined, H2O2 (10(-6)-10(-3) M) elicited an outward current at a holding potential of -40 mV and enhanced the frequency of the spontaneous transient outward current (STOC). In 20 cells the outward current was preceded by a small inward current. In the other cells, H2O2 elicited only an inward current or did not affect the background current. 4. In Ca2+ free solution the action of H2O2 on the resting muscle tone, STOCs, background current and on the current induced by ramp depolarization was significantly reduced. 5. H2O2 (10(-4) M) increased the intracellular ionized calcium concentration both in the absence and presence of external Ca2+. However, the effect developed faster and was of a higher amplitude in the presence of external Ca2+. 6. These results suggest that H2O2 increases intracellular Ca2+, with a subsequent augmentation of stimulation-evoked contractions, and enhances Ca2+ and voltage-sensitive potassium conductance.

Animals↗

PubMed1997

The electrical properties and responses to nerve stimulation of the proximal urethra of the male rabbit.

OBJECTIVE: To identify the nature of neurotransmitters acting on the smooth muscle cells of the proximal urethra and the electrical activity underlying the mechanical responses to nerve stimulation. MATERIALS AND METHODS: The electrical activity of longitudinal strips of proximal urethra obtained from male rabbits was recorded with microelectrode and double sucrose-gap techniques. Intramural nerves were stimulated with 200 microseconds pulses. Drugs which selectively affected neurotransmission were added to the perfusing fluid. RESULTS: The mean resting potential of smooth muscle cells was -39 mV and they had infrequent spontaneous action potentials. The frequency was increased by noradrenaline without depolarization; ATP produced depolarization with increased action-potential frequency. Small (< or = 16 mV) spontaneous depolarizations and hyperpolarizations could be recorded from < 50% of cells; large (< or = 40 mV) hyperpolarizations also occurred. Electrical field stimulation evoked excitatory and inhibitory junction potentials (EJPs and IJPs). Most EJPs reached a maximum within 500 ms, decayed with a time-constant of 200-300 ms and were blocked by alpha, beta-methylene ATP. IJPs had a latency of > 1 s and showed much variation in amplitude and duration. IJPs could still be recorded in the presence of N-nitro-L-arginine methyl ester (L-NAME). In the double sucrose-gap, depolarization and associated contraction were reduced by alpha, beta-methylene ATP. Further reduction occurred with phentolamine and the remaining response was blocked by atropine. A large hyperpolarization could occur in response to a single stimulus but this decreased progressively with repeated stimulation. The hyperpolarization was partially blocked by L-NAME. CONCLUSIONS: The proximal urethra receives excitatory innervation involving three neurotransmitters, i.e. ATP, acetylcholine and noradrenaline, and inhibition is associated with hyperpolarization which results at least in part from action of non-nitrergic nerves.

Action Potentials↗

PubMed1996

Angiotensin II attenuates vascular contractility in the rabbit mesenteric artery.

We observed the effects of angiotensin II (AII) on the contractile response and the Ca2+ transient induced by high K+ solution in the rabbit mesenteric artery. In the control condition, the repeated application of high K+ solution with 90 min interval induced a gradually increasing contraction, which was accompanied with a significant elevation of the intracellular calcium concentration ([Ca2+]i). Treatment of the tissue with AII for one to two hours abolished the incremental response of the contraction. The change in [Ca2+]i induced by high K+ solution, however, was not significantly different with and without treatment with AII. Pretreatment of the tissue with actinomycin D abolished the inhibitory action of AII on the incremental contraction, indicating the involvement of a transcriptional process. These results indicate that AII impairs vascular contractility through the modulation of Ca(2+)-sensitivity of the contractile machinery.

Angiotensin II↗

PubMed1994

Inhibition of capacitative Ca2+ entry by a Cl- channel blocker in human endothelial cells.

We have used the patch clamp technique in combination with intracellular calcium measurements to measure simultaneously Ca2+ entry and ionic currents activated by emptying of intracellular Ca2+ stores (capacitative Ca2+ entry and Ca2+ release-activated Ca2+ currents, CRAC) in human endothelial cells from umbilical veins. Intracellular stores were depleted of Ca2+ by preincubating endothelial cells for 20 minutes with 2 microM thapsigargin in Ca(2+)-free solution. Reapplication of 10 mM [Ca2+]e evoked an increase in [Ca2+]i indicating Ca2+ influx after the thapsigargin-induced store depletion (capacitative Ca2+ entry), however no measurable CRAC could be detected. The increase in [Ca2+]i after [Ca2+]e resubmission was substantially reduced in the presence of 50 microM NPPB (5-nitro-2-(3-phenylpropylamino)-benzoic acid) from 0.77 +/- 0.25 microM to 0.2 +/- 0.06 microM (n = 6) at a holding potential of -40 mV. Estimates of the capacitative Ca2+ entry at various membrane potentials from the first time derivative of the Ca2+ transients showed a highly inwardly rectifying I-V curve with a Ca2+ inward current amplitude of 1.0 +/- 0.3 pA (membrane capacitance 59 +/- 9 pF, n = 8) at -80 mV. This current amplitude was decreased to 0.32 +/- 0.12 pA (n = 6) in the presence of 50 microM NPPB. This corresponds to a decrease in the Ca2+ permeability of the endothelial cell membrane from 0.15 x 10(-8) cm/s (control) to 0.06 x 10(-8) cm/s (50 microM NPPB).

Calcium↗

PubMed1994

Amplitude modulation of Ca2+ signals induced by histamine in human endothelial cells.

We have addressed the problem of whether the agonist concentration sensed by endothelial cells is encoded by the sustained rise of the intracellular Ca2+ concentration ([Ca2+]i) or by the frequency of intracellular Ca2+ oscillations. Single or confluent endothelial cells from umbilical veins were stimulated for 15 min with histamine (0.03 to 100 mumol/l), and the concomitant changes in [Ca2+]i were measured with fura-2/AM. Application of histamine at concentrations above 0.1 mumol/l resulted always in a fast spike of [Ca2+]i, followed by a slow decline to a sustained plateau level, which depends on the presence of extracellular Ca2+. At the same time of the development of this plateau phase, quenching of the fura-2/AM signal occurred during agonist stimulation in a Ca(2+)-free, 1.5 mmol/l Mn2+ containing solution, indicating influx of divalent cations during this time. From 48 cells in 1.5 mmol/l [Ca2+]e we obtained a close relation between histamine concentration and time integral of [Ca2+]i taken over the 15 min recording of the plateau [Ca2+]i. The half-maximal increase in the integral of [Ca2+]i was at 0.7 mumol/l for solitary cells, 1.2 mumol/l for clustered cells and 1.2 mumol/l for the plateau Ca2+ level. Repetitive Ca2+ spikes or Ca2+ oscillations appeared only in 16 out of 48 cells, but their frequency was not correlated to the agonist concentration. Ca2+ oscillations were only observed in a concentration window between 0.1 and 1 mumol/l histamine, both in single and in clustered endothelial cells. Our results indicate that coding of the agonist concentration in endothelial cells is not related to the frequency of Ca2+ oscillations, but is closely correlated with the plateau level of intracellular Ca2+.

Calcium↗

PubMed1994

Mechanosensitive Ca2+ transients in endothelial cells from human umbilical vein.

We have investigated the changes in intracellular calcium concentration ([Ca2+]i) in human endothelial cells induced by mechanical stretch due to osmotic cell swelling. Hypotonic solutions also activate a Cl- conductance that has been described elsewhere and mainly serves to clamp the membrane potential at negative values to provide a driving force for Ca2+ influx. The increase in [Ca2+]i caused by hypotonic solutions is due to release from inositol-1,4,5-trisphosphate-sensitive Ca2+ pools and a subsequent Ca2+ influx, apparently activated by store depletion. These changes in [Ca2+]i are completely abolished if the phospholipase A2 (PLA2) activity is inhibited by either 4-bromophenacyl bromide or cyclosporin A. Arachidonic acid, applied either extracellularly or intracellularly via the patch pipette, mimics the mechanosensitive response even in cells with blocked PLA2. Metabolites of the lipo- and cyclooxygenase pathways can be excluded. Phospholipase C activation and the protein kinase A pathway are not involved in this mechanical response. Although no specific pharmacological tools for probing the role of PLA2 are available, our evidence suggests that mechanosensitivity in endothelial cells may be modulated by arachidonic acid.

Arachidonic Acid↗

PubMed1994

Kinetics of empty store-activated Ca2+ influx in HeLa cells.

The intracellular Ca2+ indicator Indo-1 was used to monitor changes in cytosolic [Ca2+] ([Ca2+]i) in single HeLa cells upon readmission of external Ca2+ after a short incubation in Ca(2+)-free solution. HeLa cells were responsive to histamine but not to caffeine, and their histamine-sensitive store was totally depleted by a 60-min exposure to 2 microM thapsigargin. The resting [Ca2+]i in thapsigargin-treated cells was higher than in control cells and low amplitude [Ca2+]i oscillations were observed in about 20% of the cells. Readmission of external Ca2+ after a brief withdrawal of extracellular Ca2+ resulted in a transient [Ca2+]i rise, which then decayed to the same elevated [Ca2+]i measured before the Ca2+ withdrawal period. The [Ca2+]i rise was associated with an increased rate of Mn2+ entry, measured as the rate of quenching of intracellular Fura-2. The same procedure did not affect the [Ca2+]i in control cells not pretreated with thapsigargin. The amplitude of this [Ca2+]i transient in thapsigargin pretreated cells depended on the duration of prior incubation in Ca(2+)-free medium. The [Ca2+]i rise induced by elevating the extracellular [Ca2+] from 1.5 to 10 mM was more pronounced if the [Ca2+]i during the initial incubation in 1.5 mM Ca2+ was first lowered by depolarizing the cells. We conclude that an empty store stimulates a Ca2+ entry pathway consisting of two components: a continuously elevated basal leak and a second component that is transient due to the high [Ca2+]i-induced inhibition of the Ca2+ entry pathway. This inhibition and the subsequent recovery from it as the [Ca2+]i is brought to resting levels could cause the oscillatory Ca2+ entry that we recorded in a fraction of the thapsigargin-treated cells.

Biological Transport↗

PubMed1994

Cytoskeletal modulation of the response to mechanical stimulation in human vascular endothelial cells.

Possible interactions of cytoskeletal elements with mechanically induced membrane currents and Ca2+ signals were studied in human endothelial cells by using a combined patch-clamp and Fura II technique. For mechanical stimulation, cells were exposed to hypotonic solution (HTS). The concomitant cell swelling activates a Cl- current, releases Ca2+ from intracellular stores and activates Ca2+ influx. To interfere with the cytoskeleton, cells were loaded either with the F-actin-stabilizing agent phalloidin (10 mumol/l), or the F-actin-depolymerizing substance cytochalasin B (50 mumol/l). These were administered either in the bath or the pipette solutions. The tubulin structure of the endothelial cells was modulated by taxol (50 mumol/l), which supports polymerization of tubulin, or by the depolymerizing agent colcemid (10 mumol/l) both applied to the bath. Immunofluorescence experiments show that under the chosen experimental conditions the cytoskeletal modifiers employed disintegrate the F-actin and microtubuli cytoskeleton. Neither of these cytoskeletal modifiers influenced the HTS-induced Cl- current. Ca2+ release was not affected by cytochalasin B, taxol or colcemid, but was suppressed if the cells were loaded with phalloidin. Depletion of intracellular Ca2+ stores by thapsigargin renders the intracellular [Ca2+] sensitive to the extracellular [Ca2+], which is indicative of a Ca2+ entry pathway activated by store depletion. Neither cytochalasin B nor phalloidin affected this Ca2+ entry. We conclude that F-actin turnover or depolymerization is necessary for Ca2+ release by mechanical activation. The tubulin network is not involved. The Ca2+ release- activated Ca2+ entry is not modulated by the F-actin cytoskeleton.

Actins↗

PubMed1994

Responses of endothelial cells to hypotonic solutions: lack of regulatory volume decrease.

Hypotonic stress (HTS) activates a Cl- current and releases intracellular Ca2+ in vascular endothelial cells, but there is no co-activation of K(+)-channels. The concomitant increase in cell volume, as assessed from the changes in endothelial cell thickness, is not followed by a regulatory volume decrease (RVD). This lack compensation of the volume increase may be explained by the absence of a concomitant activation of a K+ outward current, resulting in an insufficient efflux of osmolytes during HTS.

Cell Size↗

PubMed1994

The volume-activated chloride current in human endothelial cells depends on intracellular ATP.

We have studied the effect of intracellular ATP on volume-activated CI(-)-currents in endothelial cells from human umbilical veins by means of the whole-cell patch-clamp technique. The run-down of this current in ruptured patches during repetitive applications of hypotonic solutions (HTS) could be significantly reduced if the cells were internally perfused with a pipette solution that contained 4 mmol/l ATP. This run-down was much less pronounced if currents were recorded using nystatin-perforated patches. The amplitude of the current was drastically reduced and its activation became slower if the cells were superfused with a glucose-free medium with 1 mmol/l KCN. Adding 4 mmol/l ATP gamma S, a poorly hydrolyzable ATP-analogue, to the patch pipette prevented run-down of the current during repetitive activations by HTS, even if the cells were superfused with glucose-free solution with 1 mmol/l KCN. It is concluded that activation of the mechanosensitive Cl- conductance in human endothelial cells requires the presence of intracellular ATP, but not its hydrolysis.

Adenosine Triphosphate↗

PubMed1994

Vasopressin responses in electrically coupled A7r5 cells.

Changes in cytosolic Ca2+ concentration ([Ca2+]i) and in membrane potential were monitored in single A7r5 smooth-muscle cells during spontaneous spiking and after arginine vasopressin stimulation. Spontaneous Ca2+ oscillations, which were associated with the occurrence of action potentials, occurred in about 90% of the confluent monolayers investigated. This spontaneous activity was synchronized amongst all the cells of the monolayer, indicating that the cells were electrically coupled. Arginine vasopressin stimulation produced a [Ca2+]i rise that was about 5 times higher than the amplitude of the spontaneous Ca2+ oscillations and resulted in a subsequent cessation of spontaneous electrical activity and associated Ca2+ spiking, which persisted after [Ca2+]i returned to baseline. Individual cells in the monolayer responded to arginine vasopressin with a different latency. Agonist-induced Ca2+ waves within one cell propagated much more slowly than spontaneous [Ca2+]i rises. We conclude that agonist-induced [Ca2+]i increases in an electrically coupled cell monolayer can be asynchronous.

Animals↗

PubMed1994

Calcium entry activated by store depletion in human umbilical vein endothelial cells.

We have used the patch clamp technique combined with simultaneous measurement of intracellular Ca2+ to record ionic currents activated by depletion of intracellular Ca(2+)-stores in endothelial cells from human umbilical veins. Two protocols were used to release Ca2+ from intracellular stores, i.e. loading of the cells via the patch pipette with Ins(1,4,5)P3, and extracellular application of thapsigargin. Ins(1,4,5)P3 (10 microM) evoked a transient increase in [Ca2+]i in cells exposed to Ca(2+)-free extracellular solutions. A subsequent reapplication of extracellular Ca2+ induced an elevation of [Ca2+]i. These changes in [Ca2+]i were very reproducible. The concomitant membrane currents were neither correlated in time nor in size with the changes in [Ca2+]i. Similar changes in [Ca2+]i and membrane currents were observed if the Ca(2+)-stores were depleted with thapsigargin. Activation of these currents was prevented and holding currents at -40 mV were small if store depletion was induced in the presence of 50 microM NPPB. This identifies the large currents, which are activated as a consequence of store-depletion, as mechanically activated Cl- currents, which have been described previously [1,2]. Loading the cells with Ins(1,4,5)P3 together with 10 mM BAPTA induced only a very short lasting Ca2+ transient, which was not accompanied by activation of a detectable current, even in a 10 mM Ca(2+)-containing extracellular solution. Also thapsigargin does not activate any membrane current if the pipette solution contains 10 mM BAPTA (ruptured patches). The contribution of Ca(2+)-influx to the membrane current during reapplication of 10 mM extracellular calcium to thapsigargin-pretreated cells was estimated from the first time derivative of the corresponding Ca2+ transients at different holding potentials. These current values showed strong inward rectification, with a maximal amplitude of 1.0 +/- 0.3 pA at -80 mV (n = 8; membrane capacitance 59 +/- 9 pF).(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗

PubMed1994

Partial calcium release in response to submaximal inositol 1,4,5-trisphosphate receptor activation.

Even a prolonged application of a submaximal dose of Ins(1,4,5)P3 is unable to release the same amount of Ca2+ from the Ins(1,4,5)P3-sensitive store as a higher dose of Ins(1,4,5)P3. Low doses of Ins(1,4,5)P3 therefore only induce a partial release of the stored Ca2+. In this review, we will focus on the mechanisms that may contribute to this behaviour. Molecular heterogeneity of the Ins(1,4,5)P3 receptor can contribute to such behaviour if all the gene products and alternatively spliced isoforms would have different functional properties and be located in different store units. We will show that the control of the Ins(1,4,5)P3 receptor by by luminal Ca2+ also contributes to the partial release behaviour; it can set the sensitivity of the Ins(1,4,5)P3 receptor and the decreasing luminal Ca2+ concentration may inhibit further release while some Ca2+ is still left in the store. It is finally possible that the Ins(1,4,5)P3 receptor may adapt to a maintained stimulus.

Animals↗