Stretching releases Ca<sup>2+</sup> from intracellular storage sites in canine cerebral arteries

1. Tissue blood flow and blood pressure are regulated by the spontaneous, myogenic, contraction developed by resistance arteries. However, the cellular mechanisms underlying myogenic contraction are not understood. In this study, the mechanisms of myogenic contraction in cerebral resistance arteries were investigated. 2. The vasoconstriction observed in response to increased pressure in cerebral resistance arteries (myogenic reactivity) was dependent on Ca2+ entry through voltage‐dependent Ca2+ channels, since it was abolished by Ca2+ removal and by dihydropyridine antagonists of voltage‐dependent Ca2+ channels. 3. Myogenic reactivity persisted in a high‐K+ saline, with reduced Ca2+, where membrane potential is presumed to be clamped. Therefore, membrane depolarization alone does not fully account for the increased voltage‐dependent Ca2+ channel opening. 4. Voltage‐dependent Ca2+ currents in single smooth muscle cells isolated from the resistance artery were substantially increased by applying positive pressure to the patch electrode evoking membrane stretch. 5. Myogenic reactivity remained unaffected by ryanodine and therefore was independent of internal ryanodine‐sensitive Ca2+ stores. 6. The myofilament Ca2+ sensitivity was not increased by elevated pressure in alpha‐toxin‐permeabilized arteries. However, pharmacological activation of protein kinase C or G proteins did increase the myofilament Ca2+ sensitivity. 7. Myogenic contraction over the pressure range 30‐70 mmHg could be accounted for by an increase in [Ca2+]i from 100 to 200 nM. 8. It is concluded that modest increases in [Ca2+]i within the range 100‐200 nM can account for that myogenic contraction, and that stretch‐evoked modulation of Ca2+ currents may contribute to the myogenic response.

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“…release from the sarcoplasmic reticulum (Tanaka, Hata, Ishiro, Ishii & Nakayama, 1994). Ryanodine was used to test this possibility.…”

Section: Resultsmentioning

confidence: 99%

Myogenic contraction by modulation of voltage‐dependent calcium currents in isolated rat cerebral arteries.

McCarron

Crichton

Langton

et al. 1997

The Journal of Physiology

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“…In rat renal arteries increased activation of phospholipase C and 1, 4, 5 inositol trisphosphate (IP 3 ) generation was seen when wall tension was increased [15]and inhibition of Ca 2+ release from the SR by ryanodine has been reported to inhibit stretch-induced contraction in canine cerebral arteries [16]and rat skeletal muscle arteries [55]. In contrast, in rat cerebral arteries and human subcutaneous arteries, pressure-induced contraction was reported to be unaffected by ryanodine or CPA [11, 43].…”

Section: Discussionmentioning

confidence: 99%

“…Activation of mechanosensitive ion channels [9, 10]subsequent to stretch has been proposed as one mechanism responsible for membrane depolarisation resulting in activation of L-type voltage-operated calcium channels (Ca v 1.2) [11], although direct effects of stretch on the opening of Ca v 1.2 have also been reported [11, 12, 13, 14]. Although most studies indicate a major role for Ca v 1.2 in the myogenic response or the response to stretch, there is some evidence that Ca 2+ released from intracellular sarcoplasmic reticulum stores may also play a role in vascular smooth muscle [15, 16]or in other cell types [17, 18]. …”

Section: Introductionmentioning

confidence: 99%

Mechanism of Contraction of Rat Isolated Tail Arteries by Hyposmotic Solutions

Wijetunge

Hughes²

2005

J Vasc Res

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Contraction induced by hyposmotic swelling was examined in rat tail arteries mounted on a myograph containing a modified Krebs physiological saline solution (PSS) containing 50 mM mannitol (300 mosm/l). Hyposmotic swelling was induced by removing mannitol. In arteries having basal tone or arteries precontracted with K⁺ or the thromboxane mimetic U-46619, removal of mannitol caused a concentration dependent contraction of rat tail arteries. Concurrent measurement of tension and intracellular calcium [Ca²⁺]_iin arteries loaded with fura-2 showed that both tension and [Ca²⁺]_i increased on exposure to a hyposmotic solution. Removal of endothelium or inhibition of nitric oxide and cyclooxygenase together did not affect contractile responses. Removal of extracellular Ca²⁺ abolished the contractile response to hyposmotic solution and NiCl₂, a nonspecific inhibitor of Ca²⁺ influx pathways, blocked the rise in [Ca²⁺]_i and tension in response to a hyposmotic solution. Verapamil and nisoldipine, inhibitors of Ca_v1.2 (L-type) calcium channels significantly reduced the contractile response to a hyposmotic solution. Addition of NiCl₂ to nisoldipine caused an additional inhibition of the response to a hyposmotic solution. Inhibition of calcium release from the sarcoplasmic reticulum by ryanodine or cyclopiazonic acid (CPA) did not cause any change in the tension response to a hyposmotic solution. CPA did not significantly inhibit the response to a hyposmotic solution in the presence of N^G-methyl-L-arginine, oxyhaemoglobin and indomethacin. We conclude that contraction induced by a hyposmotic solution is largely due to Ca_v1.2 calcium channels although other Ca²⁺ influx pathways also contribute.

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“…Nonselective cation channel activation results in entry of Na ϩ and Ca 2ϩ , causing depolarization. At the same time, intracellular Ca 2ϩ is raised, as a result both of Ca 2ϩ influx (19) and release from intracellular stores (20). This increase in Ca 2ϩ is accompanied by an increase in BK channel activity, which acts to moderate the degree of membrane depolarization (21); this is seen as a protective mechanism in limiting the degree of smooth muscle contraction such that the vessels remain patent.…”

Section: Discussionmentioning

confidence: 99%

Human Podocytes Possess a Stretch-Sensitive, Ca2+-Activated K+ Channel

Morton¹,

Hutchinson²,

Mathieson

et al. 2004

Journal of the American Society of Nephrology

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Abstract. Podocytes express many proteins characteristic of smooth muscle, such as actin and myosin. They also express receptors to several vasoactive agents, including acetylcholine and angiotensin II; these phenotypic properties suggest that podocytes are not static entities but may respond to physiologic stimuli. The electrophysiologic properties of a conditionally immortalized human podocyte cell line that expresses the specific podocyte proteins nephrin, podocin, and synaptopodin were examined by patch clamp. Channels that were highly K ϩ -selective and had a conductance of 224 Ϯ 11.5 pS in symmetrical 150 mM K ϩ solutions were identified. Channel activity was Ca 2ϩ -and voltage-dependent, being increased with an increase in Ca 2ϩ or depolarization, and inhibited by penitrem A. The conductance and voltage-and Ca 2ϩ -dependence suggest that this is the largeconductance calcium-activated K ϩ channel, BK (KC-NMA1)-this was supported by reverse transcription-PCR experiments that showed the presence of the BK encoding mRNA, along with expression of KCNMB subunit types 3 and 4. In sections of human glomeruli, immunocytochemistry revealed that BK co-localizes with the podocyte-specific protein nephrin, indicating that these channels are present in native human podocytes. In whole-cell experiments, penitrem A inhibited outward currents to the same extent as tetra-ethyl ammonium (TEA) but did not affect the membrane potential. Channel activity was also increased by applying suction to the patch pipette or by dilution of the bathing medium, indicating that these channels are stretch sensitive. Thus, these channels do not contribute to the resting membrane potential but are activated by a rise in intracellular Ca 2ϩ , membrane depolarization, cell swelling, or membrane stretch. By implication, these results suggest that podocytes may be able to respond to changes in the glomerular capillary pressure and modulate the GFR.

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Stretching releases Ca²⁺ from intracellular storage sites in canine cerebral arteries

Cited by 33 publications

References 10 publications

Myogenic contraction by modulation of voltage‐dependent calcium currents in isolated rat cerebral arteries.

Myogenic contraction by modulation of voltage‐dependent calcium currents in isolated rat cerebral arteries.

Mechanism of Contraction of Rat Isolated Tail Arteries by Hyposmotic Solutions

Human Podocytes Possess a Stretch-Sensitive, Ca2+-Activated K+ Channel

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Stretching releases Ca2+ from intracellular storage sites in canine cerebral arteries

Cited by 33 publications

References 10 publications

Myogenic contraction by modulation of voltage‐dependent calcium currents in isolated rat cerebral arteries.

Myogenic contraction by modulation of voltage‐dependent calcium currents in isolated rat cerebral arteries.

Mechanism of Contraction of Rat Isolated Tail Arteries by Hyposmotic Solutions

Human Podocytes Possess a Stretch-Sensitive, Ca2+-Activated K+ Channel

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Stretching releases Ca²⁺ from intracellular storage sites in canine cerebral arteries