Developmental changes in ryanodine- and IP<sub>3</sub>-sensitive  Ca<sup>2+</sup> pools in ovine basilar artery

Nauli, Surya M.; Williams, James M.; Akopov, Sergey E.; Zhang, Li; Pearce, William J.

doi:10.1152/ajpcell.2001.281.6.c1785

Cited by 30 publications

(37 citation statements)

References 47 publications

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“…Signal intensities were collected from individual cells, as well as from the whole cell population/monolayer. All the fluorescence measurements were corrected for autofluorescence (19).…”

Section: Discussionmentioning

confidence: 99%

Loss of Polycystin-1 in Human Cyst-Lining Epithelia Leads to Ciliary Dysfunction

Nauli

Rossetti

Kolb

et al. 2006

Journal of the American Society of Nephrology

175

179

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A "two-hit" hypothesis predicts a second somatic hit, in addition to the germline mutation, as a prerequisite to cystogenesis and has been proposed to explain the focal nature for renal cyst formation in autosomal dominant polycystic kidney disease (ADPKD) A gene mutation can result in disease through direct or indirect mechanisms. For instance, in the gain-offunction mutation, a germline mutant allele confers new or enhanced protein activity with a pathologic function, whereas a dominant-negative mutation produces an aberrant protein that interferes with the function of the normal protein..In haploinsufficiency, a loss of 50% of normal protein as a result of a mutation in one of its alleles is sufficient to cause disease. In the two-hit mechanism, the disease results from a germline mutation in one allele, followed by the subsequent acquisition of a somatic mutation in the second normal allele with no remaining functional protein.Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. PKD1 and PKD2 are the genes that encode for the polycystin-1 (PC1) and polycystin-2 (PC2) proteins, respectively. Although patients with ADPKD carry heterozygous mutations in either PKD1 or PKD2 and present 100% penetrance of cystic kidney phenotypes, fewer than 5% of nephrons form cysts. These fluid-filled cysts are lined by a single layer of epithelial cells and can occur at any site along the nephron. The presence of renal cysts in ADPKD, despite the low number, results in a gradual decline in renal function. To explain the focal nature of renal cyst formation in ADPKD, Reeders (1) proposed a "two-hit" hypothesis suggesting that a second somatic alteration to the gene, in addition to a germline mutation, is a prerequisite to the disease phenotype. Although a mechanism based on haploinsufficiency has not been excluded, somatic mutations in either PKD1 or PKD2 indeed have been found in several ADPKD cyst-lining epithelia (2-8), even though a somatic loss of other chromosomes or mutations in other loci also are found (2). These data provided hints that ADPKD is a recessive disease at the cellular level. The lack of a cellular assay for PC1 function has prevented an experimental demonstration of loss of function in cyst-lining epithelia in ADPKD.We and others have shown previously that PC1 and PC2 are localized to the primary cilia (9). The mechanosensation function of polycystins can be assayed in cultured mouse kidney epithelial cells by monitoring changes in the intracellular calcium concentration in response to fluid-flow shear stress (10). To test the loss-of-function hypothesis in ADPKD with regard to mechanosensory ability, we used the flow assay to examine shear stress-induced calcium responses in cells that were derived from a heterozygous Pkd1 mouse model. Furthermore, we

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“…Signal intensities were collected from individual cells, as well as from the whole cell population/monolayer. All the fluorescence measurements were corrected for autofluorescence (19).…”

Section: Discussionmentioning

confidence: 99%

Loss of Polycystin-1 in Human Cyst-Lining Epithelia Leads to Ciliary Dysfunction

Nauli

Rossetti

Kolb

et al. 2006

Journal of the American Society of Nephrology

175

179

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“…IP 3 binds to the endoplasmic reticulum membrane (ER) IP 3 R receptors and causes the release of Ca 2+ from intracellular pools. The ryanodin receptors (RyR), stimulated, among others, by caffeine (1,11,12) are an alternative way for the release of calcium from the ER. Contraction of vascular smooth muscle may also occur via calcium ions escaping from the extracellular space through channels in the cell membrane [receptor-operated Ca 2+ channels (ROC)] activated by ligand ANG II or PHE (13).…”

Section: Introductionmentioning

confidence: 99%

Role of acetylcholine and calcium ions in three vascular contraction models: Angiotensin II, phenylephrine and caffeine

Szadujkis-Szadurska

Grześk

Szadujkis-Szadurski

et al. 2012

Experimental and Therapeutic Medicine

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Abstract. The aim of this study was to determine the role of acetylcholine and calcium ions in modulating the vascular contraction induced by angiotensin II (ANG II), phenylephrine (PHE) and caffeine. The study was performed on perfunded Wistar rat tail arteries. The contraction caused by ANG II, PHE and caffeine with the participation of intracellular [in free physiological salt solution (FPSS)] and extracellular [in physiological salt solution (PSS), after emptying the cellular stores] pools of calcium ions and the addition of L-NNA (NOSe inhibitor) or ODQ (GC inhibitor) was studied. Then the effect of acetylcholine on the contraction responses was analyzed. ANG II, PHE and caffeine induced an increase in perfusion pressure in PSS and FPSS. Acetylcholine reduced the contraction resulting from the presence of ANG II and PHE, but not caffeine. L-NNA and ODQ abolished the spasmolytic action of acetylcholine. Both pools of calcium ions mediated the action of ANG II and PHE, and caffeine induced the contraction with the participation of calcium released from intracellular stores. The spasmolytic effect of acetylcholine on responses stimulated by ANG II and PHE indicates the participation of nitric oxide in modulating the reactivity of the arteries on the studied agonists of the metabotropic receptors. No observed acetylcholine effect on caffeine suggests that the pathway associated with nitric oxide does not interfere with the contraction induced by the ryanodin receptor.

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“…This lowered spark activity in the neonate may be due to nonaggregation of ryanodine receptors and consequential unsynchronized Ca 2ϩ release from the ryanodine-sensitive stores. Indeed, mature and immature arterial SMCs may rely on different intracellular Ca 2ϩ stores (27). Recently, we showed that the BK channels in fetal SMCs have a lower Ca 0 and, as a consequence, are more active than those in adult SMCs at a given [Ca 2ϩ ] i (18).…”

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confidence: 99%

“…These include differences in K ϩ channel expression (35), K ϩ channel activity (18,23), resting membrane potential (10), intracellular Ca 2ϩ regulation (5,24), sensitivity of contraction to [Ca 2ϩ ] i (1,12,25), and others (26,32). In the ovine fetal middle cerebral artery, contraction depends almost completely on the influx of extracellular Ca 2ϩ , whereas contraction in adult myocytes relies more on Ca 2ϩ release from intracellular Ca 2ϩ stores, including the inositol 1,4,5-trisphosphate-releasable and ryanodine-sensitive stores (1,24,27).…”

mentioning

confidence: 99%

“…BK channels respond to [Ca 2ϩ ] i in the micromolar range (15,18,33). However, in intact SMCs, global [Ca 2ϩ ] i is in the submicromolar range and appears to resist increase to micromolar concentrations (38) largely because of Ca 2ϩ sequestration and buffering (27). Moreover, BK channel activity is modulated by localized and transient Ca 2ϩ elevations originating from ryanodine receptor-regulated intracellular stores (e.g., Ca 2ϩ sparks) (34) and from activated L-type Ca 2ϩ channels (9).…”

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confidence: 99%

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Modulation of BK channel calcium affinity by differential phosphorylation in developing ovine basilar artery myocytes

Lin¹,

Hessinger²,

Pearce³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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ϩ (BK) channel activity is greater in basilar artery smooth muscle cells (SMCs) of the fetus than the adult, and this increased activity is associated with a lower BK channel Ca 2ϩ set point (Ca0). Associated PKG activity is three times greater in BK channels from fetal than adult myocytes, whereas associated PKA activity is three times greater in channels from adult than fetal myocytes. We hypothesized that the change in Ca 0 during development results from different levels of channel phosphorylation. In inside-out membrane patch preparations of basilar artery SMCs from adult and fetal sheep, we measured BK channel activity in four states of phosphorylation: native, dephosphorylated, PKA phosphorylated, and PKG phosphorylated. BK channels from adult and fetus exhibited similar voltageactivation curves, Ca 0 values, and Ca 2ϩ dissociation constants (Kd) for the dephosphorylated, PKA phosphorylated, and PKG phosphorylated states. However, voltage-activation curves of native fetal BK channels shifted significantly to the left of those of the adult, with Ca0 and Kd values half those of the adult. For the two age groups at each of the phosphorylation states, Ca0 and Kd produced linear relations when plotted against voltage at half-maximal channel activation. We conclude that the Ca0 and Kd values of the BK channel can be modulated by differential channel phosphorylation. Lower Ca0 and Kd values in BK channels of fetal myocytes can be explained by a greater extent of channel phosphorylation of fetal than adult myocytes.

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Developmental changes in ryanodine- and IP₃-sensitive Ca²⁺ pools in ovine basilar artery

Cited by 30 publications

References 47 publications

Loss of Polycystin-1 in Human Cyst-Lining Epithelia Leads to Ciliary Dysfunction

Loss of Polycystin-1 in Human Cyst-Lining Epithelia Leads to Ciliary Dysfunction

Role of acetylcholine and calcium ions in three vascular contraction models: Angiotensin II, phenylephrine and caffeine

Modulation of BK channel calcium affinity by differential phosphorylation in developing ovine basilar artery myocytes

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Developmental changes in ryanodine- and IP3-sensitive Ca2+ pools in ovine basilar artery

Cited by 30 publications

References 47 publications

Loss of Polycystin-1 in Human Cyst-Lining Epithelia Leads to Ciliary Dysfunction

Loss of Polycystin-1 in Human Cyst-Lining Epithelia Leads to Ciliary Dysfunction

Role of acetylcholine and calcium ions in three vascular contraction models: Angiotensin II, phenylephrine and caffeine

Modulation of BK channel calcium affinity by differential phosphorylation in developing ovine basilar artery myocytes

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Developmental changes in ryanodine- and IP₃-sensitive Ca²⁺ pools in ovine basilar artery