Store operated calcium channels in cerebral vasospasm.

Store operated calcium channels in cerebral vasospasm.

Field: Other

Authors: Dreja, Karl
Lindqvist, Anders
Hellstrand, Per

Address of presenting
author: Department of Physiological Sciences
Cell and Molecular Physiology
Sölvegatan 19
223 62 Lund

E-mail: karl.dreja@mphy.lu.se

Phone: 046 2220631

Fax: 046 2224546

Text of abstract: Store operated Ca2+ channels (SOC's) are widely expressed in the CNS and peripheral tissues. They are involved in the late phase Ca2+ increase observed upon stimulation of a wide variety of receptors, and are activated by emptying of intracellular Ca2+ stores. Following subarachnoidal hemorrhage a cerebral vasospasm may develop, extending over several days and causing damage to large areas of the brain. This correlates with vascular accumulation of Ca2+ and arterial damage. Firm data implicate release of endothelin, acting on the ET_A receptor in arteries, in this process. This will cause IP3 release and opening of SOC's, increasing Ca2+ inflow. L-type Ca2+ channel antagonists are not an efficient treatment of cerebral vasospasm, suggesting that other channel types contribute. To investigate the role of SOCs in vascular Ca2+ homeostasis we use fluorescent Ca2+ indicators, patch clamp and tension measurements. Long-term effects of altered Ca2+ load are studied in arterial segments cultured in vitro for 3-4 days. Exposure to vasoconstrictors or depletion of intracellular Ca2+ stores raises basal [Ca2+]_i and induces degenerative changes similar to those observed in vivo, indicating Ca2+ overload. An increased size of intracellular Ca2+ stores was observed in cultured arteries, and paralleled by a large up-regulation of SOC activity. In cultured arteries stores refilled at a fourfold higher rate than in fresh vessels, and store depletion induced large, sustained increases in basal [Ca2+]_i. Both of these effects were prevented by SOC inhibitors. We conclude that SOCs are important for controlling [Ca2+]_i in vascular cells and show a considerable plasticity which may contribute to Ca2+ overload and vascular damage during maintenance of cerebral vasospasm.

Keywords: calcium channels, smooth muscle

	Store operated calcium channels in cerebral vasospasm.
Field:	Other
Authors:	Dreja, Karl Lindqvist, Anders Hellstrand, Per
Address of presenting author:	Department of Physiological Sciences Cell and Molecular Physiology Sölvegatan 19 223 62 Lund
E-mail:	karl.dreja@mphy.lu.se
Phone:	046 2220631
Fax:	046 2224546
Text of abstract:	Store operated Ca2+ channels (SOC's) are widely expressed in the CNS and peripheral tissues. They are involved in the late phase Ca2+ increase observed upon stimulation of a wide variety of receptors, and are activated by emptying of intracellular Ca2+ stores. Following subarachnoidal hemorrhage a cerebral vasospasm may develop, extending over several days and causing damage to large areas of the brain. This correlates with vascular accumulation of Ca2+ and arterial damage. Firm data implicate release of endothelin, acting on the ET_A receptor in arteries, in this process. This will cause IP3 release and opening of SOC's, increasing Ca2+ inflow. L-type Ca2+ channel antagonists are not an efficient treatment of cerebral vasospasm, suggesting that other channel types contribute. To investigate the role of SOCs in vascular Ca2+ homeostasis we use fluorescent Ca2+ indicators, patch clamp and tension measurements. Long-term effects of altered Ca2+ load are studied in arterial segments cultured in vitro for 3-4 days. Exposure to vasoconstrictors or depletion of intracellular Ca2+ stores raises basal [Ca2+]_i and induces degenerative changes similar to those observed in vivo, indicating Ca2+ overload. An increased size of intracellular Ca2+ stores was observed in cultured arteries, and paralleled by a large up-regulation of SOC activity. In cultured arteries stores refilled at a fourfold higher rate than in fresh vessels, and store depletion induced large, sustained increases in basal [Ca2+]_i. Both of these effects were prevented by SOC inhibitors. We conclude that SOCs are important for controlling [Ca2+]_i in vascular cells and show a considerable plasticity which may contribute to Ca2+ overload and vascular damage during maintenance of cerebral vasospasm.

Keywords:	calcium channels, smooth muscle

Index

Created 2000-03-16

Department of Physiological Sciences, Lund University

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