Biomedical subjects

C L Huang

Publications and source records attributed to C L Huang.

At least 19 recordsLinked to original sources

PubMed2000

Phosphatidylinositol 4,5-bisphosphate and intracellular pH regulate the ROMK1 potassium channel via separate but interrelated mechanisms.

ROMK channels are responsible for K(+) secretion in kidney. The activity of ROMK is regulated by intracellular pH (pH(i)) with acidification causing channel closure (effective pK(a) approximately 6.9). Recently, we and others reported that a direct interaction of the channels with phosphatidyl-4,5-bisphosphate (PIP(2)) is critical for opening of the inwardly rectifying K(+) channels. Here, we investigate the relationship between the mechanisms for regulation of ROMK by PIP(2) and by pH(i). We find that disruption of PIP(2)-ROMK1 interaction not only decreases single-channel open probability (P(o)) but gives rise to a ROMK1 subconductance state. This state has an increased sensitivity to intracellular protons (effective pK(a) shifted to pH approximately 7.8), such that the subconductance channels are relatively quiescent at physiological pH(i). Open probability for the subconductance channels can then be increased by intracellular alkalinization to supra-physiological pH. This increase in P(o) for the subconductance channels by alkalinization is not associated with an increase in PIP(2)-channel interaction. Thus, direct interaction with PIP(2) is critical for ROMK1 to open at full conductance. Disruption of this interaction increases pH(i) sensitivity for the channels via emergence of the subconductance state. The control of open probability of ROMK1 by pH(i) occurs via a mechanism distinct from the regulation by PIP(2).

Amino Acid Substitution↗

PubMed2000

A novel four base-pair deletion within the Agamma-GLOBin gene promoter associated with slight increase of Agamma expression in adult.

We studied a Chinese family and revealed 5.4% and 3.2% fetal hemoglobin (HbF) with advantageously Agamma type in the mother and the daughter, respectively, using alkali denaturation assay and urea-Triton-acrylamide gel electrophoresis and high-performance liquid chromatography. The father's HbF was less than 0.5%. Large deletion was not observed within the beta-globin gene cluster by restriction endonuclease mapping. Characterization by the polymerase chain reaction (PCR) and DNA sequencing demonstrated the mother is a homozygote with a novel four base-pair "AAGC" (-226 to -223) deletion within the Agamma-globin gene promoter and the daughter is a heterozygote with this deletion. The deletion was not detected in the father. No any mutations were identified in the Ggamma promoter of all the subjects studied. We propose that the small deletion is associated with the slight increase of Agamma gene expression in adult.

Adult↗

PubMed2000

The K-ras gene regulates vascular endothelial growth factor gene expression in non-small cell lung cancers.

Tumor angiogenesis is an essential step for tumor cell growth, progression and metastasis. Vascular endothelial growth factor (VEGF) is mitogen specific for endothelial cells, and therefore is believed to play a key role in tumor angiogenesis. However, the mechanisms underlying the regulation of VEGF expression remain virtually unknown and the only major regulator of VEGF expression has been reported to be hypoxia. Recently, it was reported that a mutant p53 in#duced the expression of VEGF mRNA, and that wild-type p53 down-regulated endogenous VEGF mRNA levels. In contrast, it has also been reported that mutant ras oncogenes were associated with the marked up-regulation of VEGF in transformed epithelial cells. Based on these results, we performed a retrospective study of the p53 and K-ras genes status and VEGF gene expression in the tumor tissues from 181 patients with non-small cell lung cancer using SSCP, sequencing, RT-PCR and immunohistochemical techniques. Forty-six carcinomas (25.4%) were evaluated as having high VEGF expression, and 135 tumors (74.6%) had low VEGF expression. Of the 181 primary NSCLC studied, 63 carcinomas (34.8%) contained mutations of p53, whereas only 14 carcinomas (7.7%) had mutations of K-ras. There were no significant relationships between VEGF expression and p53 status or each mutant exon of p53. In contrast, a significant difference was found between VEGF expression and K-ras status. Of the 14 tumors with mutant K-ras genes, 7 cases (50.0%) had high VEGF expression whereas only 39 of the 167 tumors with wild-type K-ras (23.4%) had high VEGF expression (p=0.0278). The mean VEGF conservation rate for the 14 tumors with mutant K-ras genes was 0.77+/-0.58 and the rate of the 167 tumors with wild-type K-ras genes was 0.49+/-0.46 (p=0. 0350). Moreover, the overall survival rate of patients with high VEGF expression was lower than patients with low VEGF expression (45.7% vs 60.7%, p=0.0419). On the other hand, there was no significant difference in the overall survival rate between patients with a mutant p53 and those with a wild-type p53; there was also no difference in the overall survival between patients with a mutant K-ras and those with a wild-type K-ras. The Cox regression model analysis indicated that three variables, VEGF status, K-ras status and nodal status, were found to be significant indicators for prognosis (p=0.0236, p=0.0172 and p<0.0001, respectively). Our data suggest that a high expression of VEGF in lung cancer may be associated with a poor prognosis. This may be a clue to improving lung cancer diagnoses and therapies aimed at inhibiting tumor angiogenesis due to VEGF.

Adult↗

PubMed1999

GABAergic organization of the cat medial geniculate body.

A study of neurons and processes (puncta) immunolabeled by antibodies to gamma-aminobutyric acid (GABA) or glutamic acid decarboxylase was undertaken in the medial geniculate body of the adult cat. The proportion and types of GABAergic cells were determined with high resolution methods, including postembbedding immunocytochemistry on semithin plastic sections. A second goal was to draw parallels and differences between the auditory thalamus and other thalamic nuclei. Finally, the types of GABAergic puncta and their concentration in the three major subdivisions of the medial geniculate body were analyzed. The results were that (1) each division had many GABAergic neurons, averaging approximately 26% of the neuronal population; (2) the ventral division had the highest proportion of these cells (33%), the medial division the fewest (18%), and the dorsal division was intermediate (26%); (3) there was a gradient in the proportion of GABAergic neurons, i.e., the ventral and medial division values increased caudorostrally, whereas the value in the dorsal division declined; (4) the predominant GABAergic cell type in each division was a small neuron with a soma approximately 10-12 microm in diameter; (5) a small population of much larger GABAergic neurons was present mainly in the dorsal division; (6) in addition to the fine, granular puncta in each division, a type of giant GABAergic puncta was found only in the dorsal division nuclei. The results obtained with the two antibodies were essentially identical. These findings suggest a structural basis for qualitative differences in the distribution of GABAergic processing within the medial geniculate complex. The GABAergic arrangement in the ventral division was stereotyped, with only one type of putative GABAergic interneuron, and the puncta were correspondingly homogeneous. In contrast, the dorsal division had two types of GABAergic neurons, and the giant GABAergic puncta represent a new substrate for inhibitory interactions. The medial division also had more than one type of GABAergic neuron and a slightly lower concentration of puncta. These qualitative and quantitative distinctions suggest a morphologic basis for possible differences in inhibitory processing among medial geniculate body subdivisions.

Animals↗

PubMed1999

Two systems of giant axon terminals in the cat medial geniculate body: convergence of cortical and GABAergic inputs.

The thalamus plays a critical role in processing sensory information that involves interactions between extrinsic connections and intrinsic circuitry. Little is known regarding how these different systems might interact. We found an unexpected nuclear convergence of two types of giant axon terminals, each of which must have independent origins, in the dorsal division of the cat medial geniculate body. The first class of giant terminal was labeled after injections of biotinylated dextran amines (BDA) in seven auditory cortical areas. A second type was found in sections immunostained for gamma-aminobutyric acid (GABA); these endings had the same nuclear distribution, and they were numerous. The origin of this GABAergic terminal is unknown. The giant corticothalamic terminals were presumably those described in prior accounts using different tracers (Rouiller and de Ribaupierre [1990] Neurosci. Lett. 208:29-35; Ojima [1994] Cerebral Cortex 6:646-663), but with BDA they are labeled more fully. Clusters of such endings were often linked, and hundreds may occur in a single section. Their boutons formed a substantial proportion of the corticothalamic population. Other types of corticogeniculate axon terminals were also labeled, including two kinds that are much smaller and that match closely the classical descriptions of corticothalamic axons. The giant GABAergic endings were found in all dorsal division nuclei and in thalamic visual nuclei such as the lateral posterior nucleus. Like the giant cortical endings, the giant GABAergic terminals often encircled large, pale, immunonegative profiles that may be dendritic. This implies a close spatial, and perhaps a close functional, relationship between the populations of giant axon terminals. Insofar as physiological studies found that pharmacological inactivation of rat somatic sensory cortex suppresses peripheral information transmission through the posterior thalamus, corticofugal input may be essential for normal processing (Diamond et al. [1992] J. Comp. Neurol. 319:66-84). Our findings suggest that the giant corticothalamic endings could play an important role in descending control. Perhaps they are counterbalanced by a GABAergic system and affect thalamic oscillations implicated in shifts in vigilance and attention.

Afferent Pathways↗

PubMed1999

Cortical spreading depression in the gyrencephalic feline brain studied by magnetic resonance imaging.

1.Time-lapse diffusion-weighted magnetic resonance imaging (DWI) was used to detect and characterize complex waves of cortical spreading depression (CSD) evoked with KCL placed upon the suprasylvian gyrus of anaesthetized cats. 2. The time-lapse representations successfully demonstrated primary CSD waves that propagated with elliptical wavefronts selectively over the ipsilateral cerebral hemispheres with a velocity of 3.8 +/- 0.70 mm min(-1) (mean +/- S.E.M. of 5 experiments). 3. In contrast, the succeeding secondary waves often remained within the originating gyrus, were slower (velocity 2.0 +/- 0.18 mm min(-1), more fragmented and varied in number. 4. Computed traces of the apparent diffusion coefficients (ADCs) showed negative deflections followed by monotonic decays (amplitudes: primary wave, -19.9 +/- 2.8%; subsequent waves, -13.6 +/- 1.9% duration at half-maximal decay, 150-200 s) when determined from regions of interest (ROIs) through which both primary and succeeding CSD waves propagated. 5. The passage of both the primary and the succeeding waves often correlated with transient DC potential deflections recorded from the suprasylvian gyrus. 6. The detailed waveforms of the ADC and the T2*-weighted (blood oxygenation level-dependent: BOLD) traces showed a clear reciprocal correlation. These imaging features that reflect disturbances in cellular water balance agree closely with BOLD measurements that followed the propagation velocities of the first and subsequent CSD events. They also provide a close physiological correlate for clinical observations of cortical blood flow disturbances associated with human migraine.

Anesthesia↗

PubMed1999

M phase phosphorylation of cytoplasmic dynein intermediate chain and p150(Glued).

To understand how the dramatic cell biological changes of oocyte maturation are brought about, we have begun to identify proteins whose phosphorylation state changes during Xenopus oocyte maturation. Here we have focused on one such protein, p83. We partially purified p83, obtained peptide sequence, and identified it as the intermediate chain of cytoplasmic dynein. During oocyte maturation, dynein intermediate chain became hyperphosphorylated at the time of germinal vesicle breakdown and remained hyperphosphorylated throughout the rest of meiosis and early embryogenesis. p150(Glued), a subunit of dynactin that has been shown to bind to dynein intermediate chain, underwent similar changes in its phosphorylation. Both dynein intermediate chain and p150(Glued) also became hyperphosphorylated during M phase in XTC-2 cells and HeLa cells. Thus, two components of the dynein-dynactin complex undergo coordinated phosphorylation changes at two G2/M transitions (maturation in oocytes and mitosis in cells in culture) but remain constitutively in their M phase forms during early embryogenesis. Dynein intermediate chain and p150(Glued) phosphorylation may positively regulate mitotic processes, such as spindle assembly or orientation, or negatively regulate interphase processes such as minus-end-directed organelle trafficking.

Animals↗

PubMed1999

Regulation of ROMK1 channel by protein kinase A via a phosphatidylinositol 4,5-bisphosphate-dependent mechanism.

ROMK inward-rectifier K+ channels control renal K+ secretion. The activity of ROMK is regulated by protein kinase A (PKA), but the molecular mechanism for regulation is unknown. Having found that direct interaction with membrane phosphatidylinositol 4, 5-bisphosphate (PIP2) is essential for channel activation, we investigate here the role of PIP2 in regulation of ROMK1 by PKA. By using adenosine-5'-[gamma-thio]triphosphate) (ATP[gammaS]) as the substrate, we found that PKA does not directly activate ROMK1 channels in membranes that are devoid of PIP2. Rather, phosphorylation by PKA + ATP[gammaS] lowers the concentration of PIP2 necessary for activation of the channels. In solution-binding assays, anti-PIP2 antibodies bind PIP2 and prevent PIP2-channel interaction. In inside-out membrane patches, antibodies inhibit the activity of the channels. PKA treatment then decreases the sensitivity of ROMK1 for inhibition by the antibodies, indicating an enhanced interaction between PIP2 and the phosphorylated channels. Conversely, mutation of the PKA phosphorylation sites in ROMK1 decreases PIP2 interaction with the channels. Thus, PKA activates ROMK1 channels by enhancing PIP2-channel interaction.

Adenosine Triphosphate↗

PubMed1999

A comparative study of acquisition schemes for diffusion tensor imaging using MRI.

This study has investigated the effects of the selection of the diffusion-weighted (DW) gradient directions on the precision of a diffusion tensor imaging (DTI) experiment. The theoretical analysis provided a quantitative framework in which the noise performance of DTI schemes could be assessed objectively and for the development of novel DTI schemes, which employ multiple DW gradient directions. This generic framework was first applied to the examination of two commonly used DTI schemes, which employed 6 DW gradient directions and hitherto were used indiscriminately under the sole condition of noncollinearity. It was then used to design and assess a novel 12-DW-gradient-direction DTI protocol, which employed the same total number of DW acquisitions as the two conventional schemes (12). This theoretical investigation was then corroborated using rigorous simulation and DTI experiments on both an isotropic phantom and a healthy human brain. Both the theoretical and the experimental analysis demonstrated that the two conventional schemes showed a significantly different noise performance and that use of the new multiple-DW-gradient-direction scheme clearly improved the precision of the DTI measurements.

Anisotropy↗

PubMed1999

Is modified in situ vaginal wall sling operation the treatment of choice for recurrent genuine stress incontinence?

PURPOSE: We evaluate objectively the results of a modified in situ vaginal wall sling operation for recurrent genuine stress incontinence and whether it is a substitute for the traditional sling procedure. MATERIALS AND METHODS: A total of 23 patients with urodynamically proved recurrent genuine stress urinary incontinence were recruited in this study. Patients were treated with a modified needle urethropexy technique using an island of in situ vaginal skin as a sling to support the bladder neck and urethra. Surgical outcome was evaluated subjectively and objectively at a median of 15 months. A total of 42 patients who underwent a traditional polytetrafluoroethylene sling operation served as controls. RESULTS: The cure rate of the vaginal wall sling operation was 34.8% by objective assessment, which was lower than that of the traditional sling procedure (88.1%, p <0.05). The subjective success rate demonstrated the same results (vaginal sling 60.9% versus traditional sling 92.9%, p <0.05). The risk factors for operation failure were lower maximal urethral pressure, lower urethral closing pressure, narrow vaginal capacity and previous anterior colporrhaphy or a Stamey operation (all p <0.05). In 3 cases suburethral epithelial inclusion cysts were specific complications of the operation. There was no prolonged urinary retention or urethral erosion. CONCLUSIONS: Based on our results, we do not believe that the vaginal wall sling operation should be recommended for all recurrent genuine stress urinary incontinence cases and especially not for those with factors predictive of surgical failure. Further studies are needed to investigate and clarify the possible causes of failure.

Female↗

PubMed1999

Design of biplanar gradient coils for magnetic resonance imaging of the human torso and limbs.

A method is described for design of gradient coils of unconventional geometry for MRI that is based on the superpositions of magnetic fields arising from individual current elements calculated by the Biot-Savart Law. Use of an optimization method based on a genetic algorithm enables a wide diversity in the shapes of coil that can be modeled. To exemplify this a two axis, biplanar gradient set is presented; this geometry offers good access for rectangular objects whilst holding the coils closer to the region of interest than is possible for cylindrical configurations. The inner dimensions of the gradient set were 40.0 x 24.4 x 40.0 cm and the gradient efficiencies were 0.3 and 0.4 mT m(-1) A(-1) in the z- and y- directions respectively over a 15 cm diameter region. Correction of signals arising from regions for which gradient linearity was not optimized was successful for the monotonic region within the set; the largest cuboid from which the MR signal could be processed to produce an undistorted image is of dimensions 36.3 x 17.2 x 24.4 cm.

Algorithms↗

PubMed1999

The reduction of the sorting bias in the eigenvalues of the diffusion tensor.

One of the most intrinsic quantities when measuring the diffusion properties of a system is the set of principal diffusivities, which represents diffusion along the fibre axes. System noise is a well-known cause of systematic sorting bias when closely spaced diffusivities are ordered according to their magnitude and leads to their inaccurate estimation. This paper describes a new method for the ordering of the principal diffusivities in which local fibre directional coherence was used as a basis for sorting. The method was applied and tested in computer simulations and experimental data acquired in an isotropic water phantom and healthy human brain. Our results demonstrate that this method leads to significant reduction in the sorting bias in comparison to other techniques and thus a more accurate estimation of the eigenvalues. The method is advantageous over other proposed alternatives to the conventional magnitude sorting method because it is not reliant on a large region-of-interest averaging scheme.

Anisotropy↗

PubMed1999

A study of rotationally invariant and symmetric indices of diffusion anisotropy.

This study investigated the properties of a class of rotationally invariant and symmetric (relative to the principal diffusivities) indices of the anisotropy of water self-diffusion, namely fractional anisotropy (FA), relative anisotropy (RA), and volume ratio (VR), with particular emphasis to their measurement in brain tissues. A simplified theoretical analysis predicted significant differences in the sensitivities of the anisotropy indices (AI) over the distribution of the principal diffusivities. Computer simulations were used to investigate the effects on AI image quality of three magnetic resonance (MR) diffusion tensor imaging (DTI) acquisition schemes, one being novel: the schemes were simulated on cerebral model fibres varying in shape and spatial orientation. The theoretical predictions and the results of the simulations were corroborated by experimentally determined spatial maps of the AI in a normal feline brain in vivo. We found that FA mapped diffusion anisotropy with the greatest detail and SNR whereas VR provided the strongest contrast between low- and high-anisotropy areas at the expense of increased noise contamination and decreased resolution in anisotropic regions. RA proved intermediate in quality. By sampling the space of the effective diffusion ellipsoid more densely and uniformly and requiring the same total imaging time as the published schemes, the novel DTI scheme achieved greater rotational invariance than the published schemes, with improved noise characteristics, resulting in improved image quality of the AI examined. Our findings suggest that significant improvements in diffusion anisotropy mapping are possible and provide criteria for the selection of the most appropriate AI for a particular application.

Animals↗

PubMed1999

Cardiac glycosides inhibit detubulation in amphibian skeletal muscle fibres exposed to osmotic shock.

It has recently been suggested that the 'vacuolation' of the transverse tubular system that follows the imposition of an osmotic shock is a component process in the eventual 'detubulation' of amphibian skeletal muscle. However, such a hypothesis requires net fluid transfers from the intracellular space into the lumina of the transverse tubules against the prevailing transmembrane osmotic gradients. The present experiments tested the effects of cardiac glycosides on the consequences of established osmotic protocols known reliably to achieve high levels of both detubulation and vacuolation in Rana temporaria sartorius muscle. Tubular isolation (detubulation) was assessed through electrophysiological observations of the abolition or otherwise of the after-depolarisation components of muscle action potentials. Vacuolation was assessed by stereological estimation of the volume fraction of muscle that was occupied by fluorescence-labelled vacuoles observed using confocal microscopy. Introduction of ouabain in the osmotic shock solutions sharply reduced such measures of vacuolation from 48.5 +/- 3.6% (mean +/- SEM; n = 70) to 12.1 +/- 2.7% (n = 190) of the total fibre volume. This was accompanied by sharp reductions in the incidence of detubulation (detubulation index reduced from 96.3 +/- 2.6% to 0.0 +/- 0.0%). The presence of ouabain was critical at the osmotic shock stage in the procedures at which the hypertonic glycerol-containing solutions were replaced by isotonic Ca(2+)-Mg(2+)-Ringer solutions. Finally, the alternative cardiac glycosides, strophanthidine and digoxin, exerted similar effects. These findings support a scheme in which the osmotic shock initiates a metabolically dependent fluid expulsion. This distends the transverse tubules into vacuoles that in turn lead to fibre detubulation.

Action Potentials↗

PubMed1999

A new function for CD38/ADP-ribosyl cyclase in nuclear Ca2+ homeostasis.

Nucleoplasmic calcium ions (Ca2+) influence nuclear functions as critical as gene transcription, apoptosis, DNA repair, topoisomerase activation and polymerase unfolding. Although both inositol trisphosphate receptors and ryanodine receptors, types of Ca2+ channel, are present in the nuclear membrane, their role in the homeostasis of nuclear Ca2+ remains unclear. Here we report the existence in the inner nuclear membrane of a functionally active CD38/ADP-ribosyl cyclase that has its catalytic site within the nucleoplasm. We propose that the enzyme catalyses the intranuclear cyclization of nicotinamide adenine dinucleotide to cyclic adenosine diphosphate ribose. The latter activates ryanodine receptors of the inner nuclear membrane to trigger nucleoplasmic Ca2+ release.

3T3 Cells↗

PubMed1999

Modulation of dopamine transporter activity by nicotinic acetylcholine receptors and membrane depolarization in rat pheochromocytoma PC12 cells.

To elucidate the regulation of the rat dopamine transporter (rDAT), we established several PC12 variants overexpressing the rDAT. Treating these cells with a nicotinic agonist (1,1-dimethyl-4-phenylpiperazinium iodide, 30 microM) depolarized the plasma membrane potential from -31 +/- 2 to 43 +/- 5 mV and inhibited rDAT activity significantly in a calcium- and protein kinase C-independent manner. Membrane depolarization by a high external K+ concentration or two K+ channel blockers (tetraethylammonium hydroxide and BaCl2) also resulted in a marked inhibition of rDAT activity. Such inhibition of dopamine uptake is due to a reduction in Vmax, with no marked effect on the Km for dopamine. The potency of cocaine in inhibiting dopamine uptake was not significantly altered, whereas that of amphetamine was slightly enhanced by membrane depolarization. Removing extracellular Ca2+ or blocking the voltage-sensitive L-type calcium channels using nifedipine did not exert any significant effect on the inhibition of rDAT activity by depolarization. These data confirm that calcium influx on depolarization is not required for inhibition of the rDAT. Collectively, our data suggest that rDAT activity can be altered by a neurotransmitter that modulates the membrane potential, thus suggesting an exquisite mechanism for the fine-tuning of dopamine levels in the synapse.

Adrenal Gland Neoplasms↗

PubMed1999

Geometrical models of left ventricular contraction from MRI of the normal and spontaneously hypertensive rat heart.

This study develops a quantitative analysis and model for the differences in left ventricular dynamics in normal and spontaneously hypertensive rats, as determined using non-invasive magnetic resonance imaging (MRI). We emerge with a characterization of the geometrical changes in the left ventricle resulting from hypertension. In addition, the techniques we have adopted are potentially applicable to the study of other disease models for important human cardiac pathologies. A gradient-echo multislice imaging sequence (echo time 4.3 ms) achieved complete image coverage of the heart at high time resolution (13 ms) through the cardiac cycle. Cardiac anatomy in two age-matched groups of young adult (8 and 12 weeks old) normal Wistar-Kyoto (WKY, n = 8) and spontaneously hypertensive rats (SHR, n = 8) was imaged in synchrony with the electrocardiographic R wave in defined planes both parallel and perpendicular to the principal cardiac axis. The transverse left ventricular image sections were circularly symmetrical; this permitted application of different analytical models for the three-dimensional geometry of the epi- and endocardial borders. An ellipsoidal figure of revolution offered an effective description of the three-dimensional left ventricular geometry throughout the cardiac cycle in both normal WKY and SHR animals. The model successfully characterized both the dynamic changes in the shape of the left ventricle through the cardiac cycle and the pathological alterations resulting from spontaneous hypertension. The elliptical model also formed the basis of a simple stress distribution analysis. Such parametric descriptions thus provided a useful alternative to more complex finite element analyses of cardiac function. The eccentricity of the ventricle was characterized by an ellipticity factor a, where a = 1 for a sphere and a < 1 for a prolate ellipsoid. At end systole, the endocardial surface of the left ventricle gave a = 0.43+/-0.02 and 0.49+/-0.02 for the WKY and SHR animals respectively (probability, P < 0.05). At end diastole, the endocardial surface of the left ventricle gave a = 0.58+/-0.02 and 0.63+/-0.02 for the WKY and SHR animals respectively (P < 0.05). Such a difference in ventricular shape was a potential adaptation to increased blood pressure. Hypertension thus altered the left ventricular ellipticity to give a more spherical geometry compared with the normal rats.

Animals↗

PubMed1999

Emerging insights into the role of calcium ions in osteoclast regulation.

Osteoclasts are exposed to unusually high, millimolar, Ca2+ concentrations and can "sense" changes in their ambient Ca2+ concentration during resorption. This results in a sharp cystolic Ca2+ increase through both Ca2+ release and Ca2+ influx. The rise in cystolic Ca2+ is transduced finally into an inhibition of bone resorption. We have shown that a type 2 ryanodine receptor isoform, expressed uniquely in the osteoblast plasma membrane, functions as a Ca2+ influx channel, and possibly as a Ca2+ sensor. Ryanodine receptors are ordinarily microsomal membrane Ca2+ release channels. They have only recently been shown to be expressed a other sites, including nuclear membranes. At the latter site, ryanodine receptors gate nucleoplasmic Ca2+ influx. Nucleoplasmic Ca2+, in turn, regulates key nuclear processes, including gene expression and apoptosis. Here, we review potential mechanisms underlying the recognition, movement, and actions of Ca2+ in the osteoclast.

Animals↗