Ca
            <sup>2+</sup>
            Sparks and Their Function in Human Cerebral Arteries

Wellman, George C.; Nathan, David J.; Saundry, Christine M.; Pérez, Guillermo J.; Bonev, Adrian D.; Penar, Paul L.; Tranmer, Bruce I.; Nelson, Mark T.

doi:10.1161/hs0302.104089

Cited by 93 publications

(69 citation statements)

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“…The net result of Ca 2ϩ influx (associated with membrane depolarization), coupled with enhanced myofilament calcium sensitivity, is an increase in vascular tone (15,24,28). Despite the stable arterial diameter commonly observed in small pressurized cerebral arteries, recent studies in resistance arteries demonstrate great individual variability in Ca 2ϩ -signaling modalities in individual myocytes within the vascular wall, suggesting a more complicated level of signaling (33,45,48). The mechanistic basis for the observed and seemingly coordinated myogenic response, presumably via the propagation of myocyte depolarization and synchronization of constriction among individual myocytes, along the length of the artery is not fully understood.…”

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confidence: 99%

Inhibitors of gap junctions attenuate myogenic tone in cerebral arteries

Lagaud

Venkateswarlu

Knot

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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Lagaud, Guy, Venkateswarlu Karicheti, Harm. J. Knot, George J. Christ, and Ismail Laher. Inhibitors of gap junctions attenuate myogenic tone in cerebral arteries. Am J Physiol Heart Circ Physiol 283: H2177-H2186, 2002; 10.1152/ajpheart. 00605.2001.-The effects of two structurally distinct inhibitors of gap junction communication were studied by using three different forms of vasoconstriction in pressurized rat middle cerebral arteries. The sensitivity of myogenic tone (at 60 mmHg), vasopressin-induced tone (10 nM, at 20 mmHg), and depolarizing solution-induced tone (80 mM K ϩ , at 20 mmHg) to inhibition by heptanol (1.0 M to 3.0 mM) or 18␣-glycyrrhetinic acid (18␣-GA, 1.0 to 50 M) were determined. Pressure-induced myogenic tone was inhibited by heptanol (IC50 ϭ 0.75 Ϯ 0.09 mM) and 18␣-GA (ϳ30 M). Vasopressin-induced vasoconstriction was also inhibited by heptanol (IC 50 ϭ 0.4 Ϯ 0.3 mM) and 18␣-GA (Ͼ1 M). Depolarizing solution-induced vasoconstriction was less sensitive to inhibition by heptanol compared to vasopressin (P Ͻ 0.01) or pressure-induced constriction (P Ͻ 0.05). However, 18␣-GA did not inhibit depolarization-induced constriction. Sharp microelectrode experiments on isolated arteries revealed stable membrane potentials, with no detectable effect of heptanol (1 mM) or 18␣-GA (20-30 M) on the average membrane potential at 20 mmHg. However, Ϸ20% of impaled cells (5 of 28) exhibited uncharacteristic oscillations in membrane potential after pharmacological uncoupling. At 60 mmHg a Ϸ7-to 9-mV hyperpolarization and corresponding vasodilation (Ϸ50%) was observed, and the frequency of membrane potential oscillations doubled (9 of 23 cells). These data indicate that gap junctions play an important role in the maintenance and modulation of membrane potential and tone in cerebral resistance arteries.heptanol; glycyrrhetinic acid; vascular smooth muscle; resistance arteries; vasopressin and depolarization RESISTANCE ARTERIES react to increases and decreases in transmural pressure by constriction and dilation, respectively. This ability to respond to pressure in a manner independent of neurohormonal modulation (15) resides in vascular smooth muscle cells and was therefore termed a "myogenic response" (22). Currently, the mechanisms producing pressure-induced constriction are complex and not fully understood. However, elevations in pressure produce smooth muscle depolarization, which coincides with arterial constriction, and in some studies the production of spontaneous action potentials (20)(21)24). This in turn results in an inward movement of Ca 2ϩ via voltageoperated Ca 2ϩ channels. The net result of Ca 2ϩ influx (associated with membrane depolarization), coupled with enhanced myofilament calcium sensitivity, is an increase in vascular tone (15,24,28). Despite the stable arterial diameter commonly observed in small pressurized cerebral arteries, recent studies in resistance arteries demonstrate great individual variability in Ca 2ϩ -signaling modalities in individual myocytes within the vascular wall, suggesting...

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mentioning

confidence: 99%

Inhibitors of gap junctions attenuate myogenic tone in cerebral arteries

Lagaud

Venkateswarlu

Knot

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…6,7 First, calcium may play a role in vascular reactivity. 21,22 Hypocalcemia could therefore lead to higher BP because of increased arterial vascular tone. However, in this cohort, we did not observe any significant association between calcium level and BP on admission.…”

Section: Discussionmentioning

confidence: 99%

Association Between Serum Calcium Level and Extent of Bleeding in Patients with Intracerebral Hemorrhage

2017

The Journal of Emergency Medicine

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“…1995; Wellman et al. 2002). Studies to date involving the vascular effects of PVAT and adiponectin on the BK channel are based on agonist‐induced constriction – interventions which significantly increase VSMC cytoplasm with Ca 2+ through summation of waves (Wier and Morgan 2003).…”

Section: Introductionmentioning

confidence: 99%

Lack of direct effect of adiponectin on vascular smooth muscle cell BK_Ca channels or Ca²⁺ signaling in the regulation of small artery pressure-induced constriction

et al. 2017

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The aim of this study was to investigate mechanisms by which adiponectin influences vascular Ca2+ signaling, K+ channel activity and thus contractile tone of small arteries. Vasodilation to adiponectin was studied in mesenteric resistance arteries constricted with intraluminal pressure. Ca2+ signals were characterized using high speed confocal microscopy of intact arteries. Patch clamp investigated the effect of adiponectin on individual VSMC potassium (K+) channel currents. Adiponectin dilated arteries constricted with pressure‐induced tone by approximately 5% and the induced vasodilation was only transient. The dilation to adiponectin was reduced by pharmacological interruption of the Ca2+ spark/large conductance activated K+ (BK) channel pathway but from a physiological perspective, interpretation of the data was limited by the small effect. Neither Adiponectin nor the presence of intact perivascular adipose tissue (PVAT) influenced Ca2+ spark or Ca2+ wave frequency or characteristics. Studied using a perforated patch approach, Adiponectin marginally increased current through the VSMC BK channel but this effect was lost using the whole cell technique with dialysis of the cytoplasm. Adiponectin did not change the frequency or amplitude of Ca2+ spark‐induced transient outward currents (STOC). Overall, our study shows that Adiponectin induces only a small and transient dilation of pressure constricted mesenteric arteries. This vasodilatory effect is likely to be independent of Ca2+ sparks or direct BK channel activation.

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Ca ²⁺ Sparks and Their Function in Human Cerebral Arteries

Abstract: Background and Purpose-Local Ca 2ϩ release events (Ca 2ϩ sparks) caused by the opening of ryanodine-sensitive Ca

Cited by 93 publications

References 30 publications

Inhibitors of gap junctions attenuate myogenic tone in cerebral arteries

Inhibitors of gap junctions attenuate myogenic tone in cerebral arteries

Association Between Serum Calcium Level and Extent of Bleeding in Patients with Intracerebral Hemorrhage

Lack of direct effect of adiponectin on vascular smooth muscle cell BK_Ca channels or Ca²⁺ signaling in the regulation of small artery pressure-induced constriction

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Ca 2+ Sparks and Their Function in Human Cerebral Arteries

Abstract: Background and Purpose-Local Ca 2ϩ release events (Ca 2ϩ sparks) caused by the opening of ryanodine-sensitive Ca

Cited by 93 publications

References 30 publications

Inhibitors of gap junctions attenuate myogenic tone in cerebral arteries

Inhibitors of gap junctions attenuate myogenic tone in cerebral arteries

Association Between Serum Calcium Level and Extent of Bleeding in Patients with Intracerebral Hemorrhage

Lack of direct effect of adiponectin on vascular smooth muscle cell BKCa channels or Ca2+ signaling in the regulation of small artery pressure-induced constriction

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Product

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Ca ²⁺ Sparks and Their Function in Human Cerebral Arteries

Lack of direct effect of adiponectin on vascular smooth muscle cell BK_Ca channels or Ca²⁺ signaling in the regulation of small artery pressure-induced constriction