Extracellular pH, Ca
            <sup>2+</sup>
            Influx, and Response of Vascular Smooth Muscle Cells to 5-Hydroxytryptamine

Nazarov, V. M.; Aquino-DeJesus, Janette; Apkon, Michael

doi:10.1161/01.str.31.10.2500

Cited by 13 publications

(6 citation statements)

References 36 publications

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“…The tissues in which opening of Cx43 HCs by extracellular alkalinization could play relevant roles are the biliary and intestinal epithelium, where Cx43 is expressed (5,25) and cells are exposed to pH values close to or above 8.0 (21,35). Ca 2ϩ influx via Cx43 HCs might also explain the alkalinizationinduced increase in intracellular [Ca 2ϩ ] through Ca 2ϩ influx in vascular endothelial and vascular smooth muscle cells (1,42,73). Moreover, Ca 2ϩ influx through Cx43 HCs could participate in a range of undesired effects of the hypocalcemia that results from alkalemia.…”

Section: Discussionmentioning

confidence: 99%

Connexin 43 hemichannels mediate the Ca²⁺ influx induced by extracellular alkalinization

Schalper

Sánchez

Lee

et al. 2010

American Journal of Physiology-Cell Physiology

152

125

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Although alkaline pH is known to trigger Ca(2+) influx in diverse cells, no pH-sensitive Ca(2+) channel has been identified. Here, we report that extracellular alkalinization induces opening of connexin 43 hemichannels (Cx43 HCs). Increasing extracellular pH from 7.4 to 8.5, in the presence of physiological Ca(2+)/Mg(2+) concentrations, rapidly increased the ethidium uptake rate and open probability of HCs in Cx43 and Cx43EGFP HeLa transfectants (HeLa-Cx3 and HeLa-Cx43EGFP, respectively) but not in parental HeLa cells (HeLa-parental) lacking Cx43 HCs. The increase in ethidium uptake induced by pH 8.5 was not affected by raising the extracellular Ca(2+) concentration from 1.8 to 10 mM but was inhibited by a connexin HC inhibitor (La(3+)). Probenecid, a pannexin HC blocker, had no effect. Extracellular alkalinization increased the intracellular Ca(2+) levels only in cells expressing HCs. The above changes induced by extracellular alkalinization did not change the cellular distribution of Cx43, suggesting that HC activation occurs through a gating mechanism. Experiments on cells expressing a COOH-terminal truncated Cx43 mutant indicated that the effects of alkalinization on intracellular Ca(2+) and ethidium uptake did not depend on the Cx43 C terminus. Moreover, purified dephosphorylated Cx43 HCs reconstituted in liposomes were Ca(2+) permeable, suggesting that Ca(2+) influx through Cx43 HCs could account for the elevation in intracellular Ca(2+) elicited by extracellular alkalinization. These studies identify a membrane pathway for Ca(2+) influx and provide a potential explanation for the activation of cellular events induced by extracellular alkalinization.

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Section: Discussionmentioning

confidence: 99%

Connexin 43 hemichannels mediate the Ca²⁺ influx induced by extracellular alkalinization

Schalper

Sánchez

Lee

et al. 2010

American Journal of Physiology-Cell Physiology

152

125

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“…Secondly, and much more plausible, are the alterations in pH resulting from changes in P aCO 2 . VSM studies in vitro have shown that changes in extracellular pH affect endothelial function and intracellular nitric oxide (Capellini et al 2013), as well as calcium influx, but not intracellular calcium release (Nazarov et al 2000). Of particular relevance, reducing pH also reduced the rate of VSM shortening in the rat portal vein (Peiper et al 1976), which would have a direct link to the reduced F upLim we found with hypercapnia.…”

Section: Physiological Considerationsmentioning

confidence: 66%

“…), as well as calcium influx, but not intracellular calcium release (Nazarov et al . ). Of particular relevance, reducing pH also reduced the rate of VSM shortening in the rat portal vein (Peiper et al .…”

Section: Discussionmentioning

confidence: 97%

The upper frequency limit of dynamic cerebral autoregulation

Panerai

Robinson

Minhas

2019

The Journal of Physiology

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Key points Dynamic cerebral autoregulation (CA) is expressed by the temporal pattern of cerebral blood flow (CBF) recovery following a sudden change in arterial blood pressure (BP). Transfer function analysis of BP as input and CBF velocity as output can express dynamic CA through its amplitude (or gain) and phase frequency responses. The upper frequency limit (FupLim) at which dynamic CA can operate is of considerable physiological interest and can also provide additional information about worsening CA due to disease processes. In healthy subjects FupLim was strongly dependent on arterial PnormalCO2 changes induced by four different breathing manoeuvres. The considerable intersubject variability in FupLim suggests that fixed frequency bands should not be adopted for averaging values of gain and phase in studies of dynamic CA. Abstract Dynamic cerebral autoregulation (CA) can be expressed in the frequency domain by the amplitude and phase frequency responses calculated by transfer function analysis of arterial blood pressure (BP) and cerebral blood flow velocity (CBFV). We studied the effects of arterial PnormalCO2 (PnormalaCO2) on the upper frequency limit (FupLim) of these responses and its intersubject variability. Twenty‐four healthy subjects (11 female, age 36.0 ± 13.4 years) were recruited. Recordings of CBFV (transcranial Doppler ultrasound), BP (Finometer) and end‐tidal CO2 (PnormalETCO2, capnography) were performed during 5 min at rest (normocapnia) and during four breathing manoeuvres: 5% and 8% CO2 in air and hyperventilation targeting reductions of 5 and 10 mmHg compared to normocapnia. FupLim was determined by the break point of the autoregulation index (ARI) curve as a function of frequency when the phase response was gradually set to zero. The five breathing conditions led to highly significant differences in PnormalETCO2 (p < 0.0001), CBFV (P < 0.0001), ARI (p < 0.0001) and FupLim (p < 0.0001). FupLim ranged from 0.167 ± 0.036 Hz at the lowest values of hypocapnia (28.1 ± 1.9 mmHg) to 0.094 ± 0.040 Hz at the highest level of hypercapnia (41.7 ± 5.4 mmHg), showing a correlation of r = −0.53 (p < 0.001) with PnormalETCO2. These findings reinforce the key role of PnormalaCO2 in CBF regulation. The considerable intersubject variability of FupLim suggests that fixed frequency bands should not be adopted for averaging values of gain and phase in dynamic CA studies, and that the higher frequency band (0.20–0.40 Hz), in particular, does not contain relevant information about dynamic CA. Further investigations are needed to assess the information value of FupLim as a marker of dynamic CA efficiency in physiological and clinical studies.

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“…Therefore, agents acting directly on the vascular smooth muscle cell may alter tone by three mechanisms: altering intracellular Ca 2+ concentrations ([Ca 2+ ] i ), varying the sensitivity of the contractile regulatory apparatus to [Ca 2+ ] i or modulating the sensitivity to other vasoactive inputs [11] . In this context, EERMv (72 and 120 µg/mL) inhibited the concentration-response contraction of NE in a nonparallel manner and depressed the maximal response (Fig.…”

Section: Resultsmentioning

confidence: 99%

Vasorelaxant Effect of Ethanolic Extracts from M. Vulgare: Mexican Medicinal Plant as Potential Source for Bioactive Molecules Isolation

Vergara-Galicia¹,

Melina²,

Joaquín³

et al. 2013

IGJPS

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To investigate vasorelaxant effect of ethanol extracts from M. vulgare, it is part of a group of plants subjected to pharmacological and phytochemical study with the purpose of offering it as an ideal source for obtaining lead compounds for designing new therapeutic agents with potential vasorelaxant and antihypertensive effects. In this context, all extracts caused concentration-dependent relaxation in -precontracted aortic rings with and without endothelium; the most active extract was EERMv. These results suggest that secondary metabolites responsible for the vasorelaxant activity belong to a group of compounds of high polarity and the roots were the main tissues of the plant where the vasorelaxant compounds are stored. In conclusion, M. vulgare represent an ideal source for obtaining lead compounds for designing new therapeutic agents with potential vasorelaxant and antihypertensive effects. © 2011 IGJPS. All rights reserved.

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Extracellular pH, Ca ²⁺ Influx, and Response of Vascular Smooth Muscle Cells to 5-Hydroxytryptamine

Abstract: Background and Purpose-Cerebral vascular smooth muscle cells (VSMCs) contract on extracellular pH (pH o ) increases and relax on pH o decreases. These changes in tone are believed to result from changes in [Ca

Cited by 13 publications

References 36 publications

Connexin 43 hemichannels mediate the Ca²⁺ influx induced by extracellular alkalinization

Connexin 43 hemichannels mediate the Ca²⁺ influx induced by extracellular alkalinization

The upper frequency limit of dynamic cerebral autoregulation

Vasorelaxant Effect of Ethanolic Extracts from M. Vulgare: Mexican Medicinal Plant as Potential Source for Bioactive Molecules Isolation

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Extracellular pH, Ca 2+ Influx, and Response of Vascular Smooth Muscle Cells to 5-Hydroxytryptamine

Abstract: Background and Purpose-Cerebral vascular smooth muscle cells (VSMCs) contract on extracellular pH (pH o ) increases and relax on pH o decreases. These changes in tone are believed to result from changes in [Ca

Cited by 13 publications

References 36 publications

Connexin 43 hemichannels mediate the Ca2+ influx induced by extracellular alkalinization

Connexin 43 hemichannels mediate the Ca2+ influx induced by extracellular alkalinization

The upper frequency limit of dynamic cerebral autoregulation

Vasorelaxant Effect of Ethanolic Extracts from M. Vulgare: Mexican Medicinal Plant as Potential Source for Bioactive Molecules Isolation

Contact Info

Product

Resources

About

Extracellular pH, Ca ²⁺ Influx, and Response of Vascular Smooth Muscle Cells to 5-Hydroxytryptamine

Connexin 43 hemichannels mediate the Ca²⁺ influx induced by extracellular alkalinization

Connexin 43 hemichannels mediate the Ca²⁺ influx induced by extracellular alkalinization