Biomedical subjects

L Vaca

Publications and source records attributed to L Vaca.

At least 19 recordsLinked to original sources

PubMed2002

Modulation of the maitotoxin response by intracellular and extracellular cations.

The aim of the present study was to characterize the role played by intracellular and extracellular calcium and sodium on the maitotoxin (MTX) response in Chinese hamster ovary (CHO) cells. The results presented here indicated that: (1) MTX activates calcium and sodium influx in a concentration-dependent manner; (2) extracellular calcium is required for the sodium influx; (3) removal of the extracellular sodium did not prevent the MTX-induced calcium influx; (4) elevation in the intracellular calcium concentration potentiates the MTX response; and (5) MTX, at the concentrations tested, did not compromise cell viability.

Algorithms↗

PubMed2001

Isovolumetric regulation mechanisms in cultured cerebellar granule neurons.

Cultured cerebellar granule neurons exposed to gradual reductions in osmolarity (-1.8 mOsm/min) maintained constant volume up to -50% external osmolarity (pi(o)), showing the occurrence of isovolumetric regulation (IVR). Amino acids, Cl-, and K+ contributed at different phases of IVR, with early efflux threshold for [3H]taurine, D-[3H]aspartate (as marker for glutamate) of pi(o) -2% and -19%, respectively, and more delayed thresholds of -30% for [3H]glycine and -25% and -29%, respectively, for Cl- (125I) and K+ (86Rb). Taurine seems preferentially involved in IVR, showing the lowest threshold, the highest efflux rate (five-fold over other amino acids) and the largest cell content decrease. Taurine and Cl- efflux were abolished by niflumic acid and 86Rb by 15 mM Ba2+. Niflumic acid essentially prevented IVR in all ranges of pi(o). Cl--free medium impaired IVR when pi(o) decreased to -24% and Ba2+ blocked it only at a late phase of -30% pi(o). These results indicate that in cerebellar granule neurons: (i) IVR is an active process of volume regulation accomplished by efflux of intracellular osmolytes; (ii) the volume regulation operating at small changes of pi(o) is fully accounted for by mechanisms sensitive to niflumic acid, with contributions of both Cl- and amino acids, particularly taurine; (iii) Cl- contribution to IVR is delayed with respect to other niflumic acid-sensitive osmolyte fluxes (osmolarity threshold of -25% pi(o)); and (iv), K+ fluxes do not contribute to IVR until a late phase (< -30% pi(o)).

Amino Acids↗

PubMed2001

Functional expression of recombinant type 1 ryanodine receptor in insect cells.

We have investigated the biochemical properties of the rabbit ryanodine receptor type 1 (RyR1) from skeletal muscle functionally expressed in insect sf 21 cells infected with recombinant baculovirus. Equilibrium [3H]ryanodine binding assays applied to total membrane fractions from sf 21 cells expressing recombinant RyR1 showed a non-hyperbolic saturation curve (Hill coefficient = 2.1). The [3H]ryanodine binding was enhanced by 1 mM AMP-PCP and 10 mM caffeine, whereas 10 mM Mg(2+) and 5 microM ruthenium red reduced the specific binding. The dependence of [3H]ryanodine binding on ionic strength showed positive cooperativity (Hill coefficient = 2.2) with a plateau at 1 M KCl. The recombinant RyR1 showed a bell-shaped [3H]ryanodine binding curve when free [Ca(2+)] was increased, with an optimal concentration around 100 microM.Confocal microscopy studies using the Ca(2+) ATPase selective inhibitor, thapsigargin coupled to fluorescein and ryanodine coupled to Texas red demonstrated that the recombinant RyR1 and the Ca(2+) ATPase co-localize to the same intracellular membrane. No significant RyR1 fluorescence was observed at the plasma membrane.Fluo-4-loaded sf 21 cells expressing recombinant RyR1 responded to activating-low ryanodine concentrations (100 nM) or caffeine (10 mM) with a sharp rise in intracellular Ca2 followed by a sustained phase, in contrast, sf 21 cells expressing the human bradykinin type 2 receptor did not respond to ryanodine or caffeine.These results demonstrate the expression of recombinant RyR1 in sf 21 cells with functional properties similar to what has been previously reported for native RyR1 in mammalian tissues, however, some differences were observed in [3H]ryanodine binding assays compared to native rabbit RyR1. Hence, the baculovirus expression system provides a generous source of protein to accomplish structure-function studies and an excellent model to assess functional properties of wild type and mutant RyR1.

Animals↗

PubMed2000

Mutations in the S4 domain of a pacemaker channel alter its voltage dependence.

In an attempt to study the functional role of the positively charged amino acids present in the S4 segment of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels, we have introduced single and sequential amino acid replacements throughout this domain in the mouse type 2 HCN channel (mHCN2). Sequential neutralization of the first three positively charged amino acids resulted in cumulative shifts of the midpoint voltage activation constant towards more hyperpolarizing potentials. The contribution of each amino acid substitution was approximately -20 mV. Amino acid replacements to neutralize either the first (K291Q) or fourth (R300Q) positively charged amino acid resulted in the same shift (about 20 mV) towards more hyperpolarized potentials. Replacing the first positively charged amino acid with the negatively charged glutamic acid (K291E) produced a shift of approximately -50 mV in the same direction. None of the above amino acid substitutions had any measurable effect on the time course of channel activation. This suggests that the S4 domain of HCN channels critically controls the voltage dependence of channel opening but is not involved in regulating activation kinetics. No channel activity was detected in mutants with neutralization of the last six positively charged amino acids from the S4 domain, suggesting that these amino acids cannot be altered without impairing channel function.

Amino Acid Sequence↗

PubMed2000

Regulation of the human bradykinin B2 receptor expressed in sf21 insect cells: a possible role for tyrosine kinases.

The functional regulation of the human bradykinin B2 receptor expressed in sf21 cells was studied. Human bradykinin B2 receptors were immunodetected as a band of 75-80 kDa in membranes from recombinant baculovirus-infected cells and visualized at the plasma membrane, by confocal microscopy, using an antibody against an epitope from its second extracellular loop. B2 receptors, detected in membranes by [(3)H-bradykinin] binding, showed a Kd of 0.66 nmol/L and an expression level of 2.57 pmol/mg of protein at 54 h postinfection. In these cells, bradykinin induced a transient increase of intracellular calcium ([Ca(2+)](i)) in fura 2-AM loaded sf21 cells, and promoted [(35)S]-GTP(gamma)S binding to membranes. The effects of bradykinin were dose dependent (with an EC(50) of 50 nmol/L for calcium mobilization) and were inhibited by N-alpha-adamantaneacetyl-D-Arg-[Hyp(3),Thi(5,8),D-phe(7)]-Bk, a specific B2 receptor antagonist. When the B2 antagonist was applied at the top of the calcium transient, it accelerated the decline of the peak, suggesting that calcium mobilization at this point was still influenced by receptor occupation. No calcium mobilization was elicited by 1 micromol/L (Des-Arg(9))-Bk, a B1 receptor agonist that did not inhibit the subsequent action of 100 nmol/L bradykinin. No effect of bradykinin was detected in uninfected cells or cells infected with the wild-type baculovirus. Bradykinin-induced [Ca(2+)](i) mobilization was increased by genistein and tyrphostin A51. These tyrosine kinase inhibitors did not modify basal levels of [Ca(2+)](i). Homologous desensitization of the B2 receptor was observed after repeated applications of bradykinin, which resulted in attenuated changes in intracellular calcium. In addition, genistein promoted an increased response to a third exposure to the agonist when applied after washing the cells that had been previously challenged with two increasing doses of bradykinin. Genistein did not affect the calcium mobilization induced by activation of the endogenous octopamine G protein-coupled receptor or by thapsigargin. The B2 receptor, detected by confocal microscopy in unpermeabilized cells, remained constant at the surface of cells stimulated with bradykinin for 10 min, in the presence or absence of genistein. Agonist-promoted phosphorylation of the B2 receptor was markedly accentuated by genistein treatment. Phosphoaminoacid analysis revealed the presence of phosphoserine and traces of phosphothreonine, but not phosphotyrosine, suggesting that the putative tyrosine kinase(s), activated by bradykinin, could act in a step previous to receptor phosphorylation. Interestingly, genistein prevented agonist-induced G protein uncoupling from B2 receptors, determined by in vitro bradykinin-stimulated [(35)S]-GTP(gamma)S binding, in membranes from bradykinin pretreated cells. Our results suggest that tyrosine kinase(s) regulate the activity of the human B2 receptor in sf21 cells by affecting its coupling to G proteins and its phosphorylation.

Animals↗

PubMed1999

SITS blockade induces multiple subconductance states in a large conductance chloride channel.

The effect of the chloride channel blocker 4-acetamido-4-isothiocyanatostilbene-2,2-disulfonic acid (SITS) on the gating and amplitude of an endothelial chloride channel was explored using the outside-out configuration of the patch-clamp technique. Under control conditions the channel displayed two main gating modes: shut and fully open. Transitions to equally spaced subconductance states were rarely observed (less than 10 events/minute). At low concentrations (<45 microm), SITS increased the number of transitions to the three subconductance states in a concentration-dependent manner, while reducing the number of transitions to the fully open state. This effect was maintained after removing SITS from the bath solution, suggesting that the modifications in the channel induced by SITS were irreversible. All four conducting states had similar current-voltage relationships. At higher concentrations (>45 microm), SITS reduced the amplitude of all conducting states (three subconductances and fully open). This effect was fully reversible upon SITS removal from the bath solution. A half-inhibitory concentration (IC50) of 55.6 +/- 2.7 microm (+60 mV) and 66.7 +/- 2.2 (-60 mV) was obtained from the fitting to a Langmuir function. All these results are compatible with the existence of two SITS binding sites in the chloride channel: one of high affinity responsible for the increment in the number of transitions to subconductance states, and one low affinity binding site involved in the reduction of the amplitude of all conducting states.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

PubMed1999

Modulation of a calcium-activated chloride current by Maitotoxin.

The effect of Maitotoxin (MTX) on the calcium-activated chloride current (ICl-Ca) from Xenopus oocytes was studied, applying the two-electrode voltage clamp technique. MTX increased the current amplitude at all the voltages explored and reduced the time to reach the maximum current level (time to peak). At low toxin concentrations (15 pM), both effects were fully reversible. Activation of ICl-Ca by MTX was secondary to the increment in the intracellular Ca2+ concentration induced by this toxin, since incubation of the oocytes with the cell-permeant Ca2+ chelator BAPTA-AM, greatly reduced the effect of MTX on ICl-Ca. Furthermore, external chloride ions removal also diminished the MTX effect on the current, strongly suggesting that the main current activated by MTX is ICl-Ca. Subsequent applications of a fixed toxin concentration after toxin washout resulted in enhanced ICl-Ca, suggesting that the toxin effect potentiates.

Animals↗

PubMed1998

Osmotic swelling-induced changes in cytosolic calcium do not affect regulatory volume decrease in rat cultured suspended cerebellar astrocytes.

Hyposmotic swelling-induced changes in intracellular Ca2+ concentration ([Ca2+]i) and their influence on regulatory volume decrease (RVD) were examined in rat cultured suspended cerebellar astrocytes. Hyposmotic media (50 or 30%) evoked an immediate rise in [Ca2+]i from 117 nM to a mean peak increase of 386 (50%) and 220 nM (30%), followed by a maintained plateau phase. Ca2+ influx through the plasmalemma as well as release from internal stores contributed to this osmosensitive [Ca2+]i elevation. Omission of external Ca2+ or addition of Cd2+, Mn2+, or Gd3+ did not reduce RVD, although it was decreased by La3+ (0.1-1 mM). Verapamil did not affect either the swelling-evoked [Ca2+]i or RVD. Maneuvers that deplete endoplasmic reticulum (ER) Ca2+ stores, such as treatment (in Ca2+-free medium) with 0.2 microM thapsigargin (Tg), 10 microM 2,5-di-tert-butylhydroquinone, 1 microM ionomycin, or 100 microM ATP abolished the increase in [Ca2+]i but did not affect RVD. However, prolonged exposure to 1 microM Tg blocked RVD regardless of ER Ca2+ content or cytosolic Ca2+ levels. Ryanodine (up to 100 microM) and caffeine (10 mM) did not modify [Ca2+]i or RVD. BAPTA-acetoxymethyl ester (20 microM) abolished [Ca2+]i elevation without affecting RVD, but at higher concentrations BAPTA prevented cell swelling and blocked RVD. We conclude that the osmosensitive [Ca2+]i rise occurs as a consequence of increased Ca2+ permeability of plasma and organelle membranes, but it appears not relevant as a transduction signal for RVD in rat cultured cerebellar astrocytes.

Animals↗

PubMed1998

A tyrosine-rich region in the N terminus of CCR5 is important for human immunodeficiency virus type 1 entry and mediates an association between gp120 and CCR5.

Human immunodeficiency virus type 1 (HIV-1) requires the presence of specific chemokine receptors in addition to CD4 to enter target cells. The chemokine receptor CCR5 is used by the macrophage-tropic strains of HIV-1 that predominate during the asymptomatic stages of infection. Here we identify a small tyrosine-rich region of CCR5 proximal to the N-terminal cysteine that is critical for entry of macrophage-tropic and dual-tropic variants of HIV-1. HIV-1 infection of cells expressing CCR5 mutants with changes in this region was substantially reduced compared with the infection of cells bearing wild-type CCR5. Simian immunodeficiency virus (SIVmac239) entry was also ablated on a subset of these mutants but enhanced on others. These differences in virus entry were correlated with the relative ability of soluble, monomeric HIV-1 and SIVmac239 gp120 glycoproteins to bind the CCR5 mutants. These results identify a region of CCR5 that is necessary for the physical association of the gp120 envelope glycoprotein with CCR5 and for HIV-1 infection.

Animals↗

PubMed1998

Maitotoxin, a cationic channel activator.

Maitotoxin (MTX), a water soluble polyether obtained from the marine dinoflagellate Gambierdiscus toxicus is one of the entities responsible for Ciguatera, a form of seafood poisoning. This toxin is a potent activator of changes in the intracellular Ca2+ concentrations of cells from a wide variety of organisms. Evidence published in the last few years strongly suggests that this toxin has no ionophoretic activity. Molecular mechanics studies, shown for the first time in this review, models MTX as a molecular 'wire'. The present work compiles the few studies developed with electrophysiological techniques. All these reports indicate that MTX is activating a voltage independent, nonselective cationic channel, which in some preparations requires the presence of extracellular Ca2+ for channel activation. The conductance estimated from a variety of tissues is in the order of 12-40 pS. Thus far, no specific blocker has been identified for this channel. The nature of the MTX receptor remains a mistery.

Animals↗

PubMed1997

Characterization of the maitotoxin-induced calcium influx pathway from human skin fibroblasts.

Maitotoxin (MTX), a water-soluble polyether obtained from the marine dinoflagellate Gambierdiscus toxicus increased intracellular calcium in a concentration-dependent manner in fibroblasts obtained from human skin. The effect of this toxin was both saturable and of high affinity, showing an apparent half activation constant of 450 fM. The toxin did not release intracellular calcium storage compartments nor did the release of these compartments with thapsigargin or ionomycin affect the toxin response. The toxin effect was reduced significantly by pre-incubating the cells with 0.1% trypsin for 30 min, strongly suggesting that the toxin receptor is a plasmalemmal protein. The effect of MTX was partially inhibited by diphenoxylate.

Calcium↗

PubMed1997

Properties of single Drosophila Trpl channels expressed in Sf9 insect cells.

The transient receptor potential (trp)-like (trpl) gene is thought to encode an ion channel important for signal transduction in Drosophila photoreceptor cells. Consistent with this hypothesis, heterologous expression of the trpl-encoded protein (Trpl) is associated with the appearance of an outwardly rectifying, nonselective cation current. In the present study, single channels were recorded in cell-attached, inside-out, and outside-out membrane patches from Sf9 insect cells infected with recombinant baculovirus-containing trpl cDNA under control of the polyhedrin promoter. The single-channel current-voltage relationship was linear from -100 to +80 mV with a slope conductance of 89-110 pS. The probability of opening was voltage sensitive, increasing at positive potentials contributing to the outwardly rectifying properties of the whole cell currents. The single channels 1) were never observed in Sf9 cells infected with recombinant baculovirus containing the B2 bradykinin receptor cDNA or in noninfected Sf9 cells; 2) appear at the same time postinfection as the Trpl whole cell current; 3) were nonselective with respect to Na+, Ca2+, and Ba2+; 4) were blocked by 1-2 mM La3+ and Gd3+ (but not 10 microM); and 5) were blocked by 4-8 mM Mg2+. The single Trpl channel activity increased spontaneously with time after patch formation, and the activity was further increased by application of bradykinin to cells expressing both the B2 bradykinin receptor and the Trpl protein. These results suggest that this single-channel activity reflects expression of the Trpl protein and provides conclusive evidence that trpl encodes a nonselective cation channel consistent with its proposed role in Drosophila phototransduction.

Animals↗

PubMed1996

Calmodulin inhibits calcium influx current in vascular endothelium.

Utilizing the whole-cell configuration of the patch-clamp technique the effect of calmodulin (CaM) on thapsigargin-induced Ca2+ current has been studied. Addition of several concentrations of CaM to the patch pipette induced concentration-dependent inhibition of thapsigargin-induced Ca2+ current in bovine aortic endothelial cells. The effect of CaM was Ca2+ dependent and was not observed when the intracellular Ca2+ was buffered to 1 nM with EGTA. CaM produced two major effects on the thapsigargin-induced Ca2+ current. First CaM slow down activation of the current by thapsigargin from a control value of 16 +/- 5 to 31 +/- 6 s with 1 microM CaM in the pipette solution. The second effect of CaM was to reduce the current amplitude in a concentration-dependent manner. The inhibition of Ca2+ current was observed at the peak of the current and at the sustained current level. The reduction of current at the sustained level was observed 15-20 s after onset of the thapsigargin response. The half inhibitory concentration determined from these experiments was 0.1 microM. These results indicate that CaM can modulate thapsigargin-induced Ca2+ current in this endothelium, suggesting a possible role for CaM in the regulation of store-operated Ca2+ influx.

Animals↗

PubMed1996

The COOH-terminal domain of Drosophila TRP channels confers thapsigargin sensitivity.

Previous studies have shown that the Drosophila cation channels designated Trp and Trpl can be functionally expressed in Sf9 insect cells using baculovirus expression vectors. The trp gene encodes a Ca2+-permeable channel that is activated by thapsigargin, blocked by low micromolar Gd3+, and is relatively selective for Ca2+ versus Na+ and Ba2+. In contrast, trpl encodes a Ca2+-permeable cation channel that is constitutively active, not affected by thapsigargin, blocked by high micromolar Gd3+, and non-selective with respect to Ca2+, Na+, and Ba2+. The region of lowest sequence identity between Trp and Trpl occurs in the COOH-terminal domain. To test the hypothesis that this region is responsible for the differential sensitivity of these channels to thapsigargin, chimeric constructs of Trp and Trpl were created in which the COOH-terminal tail region of each protein was exchanged. The Trp construct with the Trpl COOH-tail was constitutively active, insensitive to thapsigargin, but retained selectivity for Ca2+ over Na+ and Ba2+. In contrast, the Trpl construct with the Trp COOH-tail was not constitutively active, could be activated by thapsigargin, but remained non-selective with respect to Ca2+, Ba2+, and Na+. These results suggest that the COOH-terminal domain of Trpl plays an important role in determining constitutive activity, whereas the COOH-terminal region of Trp contains the structural features necessary for activation by thapsigargin.

Amino Acid Sequence↗

PubMed1996

Noxiustoxin 2, a novel K+ channel blocking peptide from the venom of the scorpion Centruroides noxius Hoffmann.

A novel peptide called Noxiustoxin 2 (NTX2) was purified from the venom of the scorpion Centruroides noxius and characterized chemically and functionally. It is composed of 38 amino acid residues linked by three disulfide bridges and its primary structure is 61% identical to that of Noxiustoxin (NTX). It is not toxic to mice (using up to 200 micrograms/20 g mouse weight) and crustaceans (up to 30 micrograms/g of crayfish), but has a paralysing effect on crickets (30 micrograms/g animal). It displaces the binding of [125I]NTX to rat brain synaptosome membranes with a Ki of 0.1 microM, in comparison NTX has a Ki of 100 pM. Similarly, using single Ca2+ activated K+ channels of small conductance obtained from cultured bovine aortic endothelial cells it was shown that NTX2 is over two logarithm units less potent than NTX in producing 50% blockade of the probability of opening the channels. NTX2 is not recognized by a panel of six distinct monoclonal antibodies against NTX, however it is recognized by polyclonal antibodies raised in mouse, with native NTX. Primary structure comparison of both NTX and NTX2 suggests that the N-terminal segments of these peptides are important for channel affinity.

Amino Acid Sequence↗

PubMed1996

Modulation of cell membrane potential in cultured vascular endothelium.

The present study explores the role of different ionic conductances in the regulation of membrane potential under resting conditions and after bradykinin (BK) or thapsigargin (TG) stimulation of cultured bovine aortic endothelial cells. Under resting conditions, the cell membrane potential observed was -62+/- 5 mV. The main conductance under these conditions is an inwardly rectifying potassium (IRK) channel. Application of 50 nM BK induced a transient hyperpolarization to -87 +/- 4 mV followed by sustained depolarization to -35 +/- 5 mV. The transient hyperpolarization was eliminated by 1 microM noxiustoxin, a blocker of calcium-activated postassium channels (K(Ca)). the sustained depolarization induced by BK was prevented by incubating the cells with the calcium channel blocker lanthanum. TG evoked a similar response in membrane potential, with the exception that the onset of the hyperpolarization was slower compared with BK. The results presented here indicate that the cell resting potential is maintained at -62 +/- 2 mV by the IRK channel. BK or TG stimulation induces a transient hyperpolarization of approximately -20 mV produced by activation of a KCa. This hyperpolarization is followed by a sustained depolarization produced by activation of a calcium-selective channel sensitive to lanthanum.

Animals↗

PubMed1995

IP3-activated Ca2+ channels in the plasma membrane of cultured vascular endothelial cells.

Although it is clear that D-myo-inositol 1,4,5-trisphosphate (IP3) plays an important role in the activation of Ca2+ influx, the mechanisms by which this occurs remain controversial. In an attempt to determine the role of IP3 in the activation of Ca2+ influx, patch-clamp single-channel experiments in the cell-attached, inside-out, and outside-out configurations were performed on cultured bovine aortic endothelial cells (BAEC). The results presented indicate that both IP3 and intracellular Ca2+ can modulate the activity of a Ca(2+)-selective channel found in the plasma membrane of these cells. Addition of 10 microM IP3 increased channel open probability (P(o)) from a control value of 0.12 +/- 0.05 to 0.7 +/- 0.13 at a constant intracellular Ca2+ of 1 nM in excised inside-out patches. D-Myo-inositol 1,3,4,5-tetrakisphosphate at 50 microM was ineffective in altering channel P(o). Channel activity declined after approximately 2 min in the continuous presence of IP3. Three to four minutes after addition of IP3, channel P(o) was reduced from 0.7 +/- 0.2 to 0.2 +/- 0.1, indicating that an additional regulator might be required to maintain channel activity in excised patches. The channel was reversibly blocked by application of 1 microgram/ml heparin to the intracellular side of inside-out patches. This Ca(2+)-selective channel is indistinguishable from the depletion-activated Ca2+ channel we have previously described in BAEC.

Animals↗

PubMed1995

Ins(1,4,5)P3 activates Drosophila cation channel Trpl in recombinant baculovirus-infected Sf9 insect cells.

The trp-like (trpl) gene product (Trpl) is thought to form a nonselective cation channel important for signal transduction in Drosophila photoreceptor cells. This channel may be the insect homologue of mammalian channels involved in Ca2+ signal transduction. To determine the mechanism of receptor-mediated activation of Trpl, whole cell membrane currents were examined in Sf9 insect cells after infection with recombinant baculovirus. Stimulation by bradykinin increased whole cell Trpl currents three- to fivefold. Similar activation of Trpl was observed by inclusion of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in the pipette solution during whole cell recordings. These currents were 1) not seen in noninfected cells or in cells expressing only the B2 receptor, 2) mimicked by D-myo-inositol 2,4,5-trisphosphate, and 3-deoxy-3-fluoro-D-myo-inositol 1,4,5-trisphosphate, 3) not seen with D-myo-inositol 1,4-bisphosphate or D-myo-inositol 1,3,4,5-tetrakisphosphate, and 4) blocked by heparin, but not by de-N-sulfated heparin. In contrast, Trpl currents were unaffected by thapsigargin. These results demonstrate that the Trpl cation channel is activated by Ins(1,4,5)P3 in a heparin-sensitive fashion. Regulation of channel activity by Ins(1,4,5)P3 may occur by a number of mechanisms, including direct binding of Ins(1,4,5)P3 to the Trpl channel or direct physical interaction between the Ins(1,4,5)P3 receptor/Ca(2+)-release channel of the endoplasmic reticulum and the Trpl protein.

Animals↗