Ca2+handling is altered when arterial myocytes progress from a contractile to a proliferative phenotype in culture

Autor: Maria V. Pulina, Vera A. Golovina, Roberto Berra-Romani, Amparo Mazzocco-Spezzia
Rok vydání: 2008
Předmět:
Male
medicine.medical_specialty
Indoles
Time Factors
Physiology
Blotting
Western
Myocytes
Smooth Muscle
Inositol 1
4
5-Trisphosphate
Biology
Muscle
Smooth
Vascular
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Rats
Sprague-Dawley
Adenosine Triphosphate
Downregulation and upregulation
Vascular Biology
Mesenteric Artery
Superior
Caffeine
Internal medicine
medicine
Animals
Inositol 1
4
5-Trisphosphate Receptors
Myocyte
Calcium Signaling
Stromal Interaction Molecule 1
Enzyme Inhibitors
Cells
Cultured
Cell Proliferation
Fluorescent Dyes
TRPC Cation Channels
Membrane Glycoproteins
Ryanodine
Cell growth
Ryanodine Receptor Calcium Release Channel
STIM1
Cell Biology
Store-operated calcium entry
Phenotype
Rats
Up-Regulation
Sarcoplasmic Reticulum
Endocrinology
Microscopy
Fluorescence
Vasoconstriction
medicine.symptom
Fura-2
Intracellular
Zdroj: American Journal of Physiology-Cell Physiology. 295:C779-C790
ISSN: 1522-1563
0363-6143
DOI: 10.1152/ajpcell.00173.2008
Popis: Phenotypic modulation of vascular myocytes is important for vascular development and adaptation. A characteristic feature of this process is alteration in intracellular Ca2+handling, which is not completely understood. We studied mechanisms involved in functional changes of inositol 1,4,5-trisphosphate (IP3)- and ryanodine (Ry)-sensitive Ca2+stores, store-operated Ca2+entry (SOCE), and receptor-operated Ca2+entry (ROCE) associated with arterial myocyte modulation from a contractile to a proliferative phenotype in culture. Proliferating, cultured myocytes from rat mesenteric artery have elevated resting cytosolic Ca2+levels and increased IP3-sensitive Ca2+store content. ATP- and cyclopiazonic acid [CPA; a sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) inhibitor]-induced Ca2+transients in Ca2+-free medium are significantly larger in proliferating arterial smooth muscle cells (ASMCs) than in freshly dissociated myocytes, whereas caffeine (Caf)-induced Ca2+release is much smaller. Moreover, the Caf/Ry-sensitive store gradually loses sensitivity to Caf activation during cell culture. These changes can be explained by increased expression of all three IP3receptors and a switch from Ry receptor type II to type III expression during proliferation. SOCE, activated by depletion of the IP3/CPA-sensitive store, is greatly increased in proliferating ASMCs. Augmented SOCE and ROCE (activated by the diacylglycerol analog 1-oleoyl-2-acetyl- sn-glycerol) in proliferating myocytes can be attributed to upregulated expression of, respectively, transient receptor potential proteins TRPC1/4/5 and TRPC3/6. Moreover, stromal interacting molecule 1 (STIM1) and Orai proteins are upregulated in proliferating cells. Increased expression of IP3receptors, SERCA2b, TRPCs, Orai(s), and STIM1 in proliferating ASMCs suggests that these proteins play a critical role in an altered Ca2+handling that occurs during vascular growth and remodeling.
Databáze: OpenAIRE
Externí odkaz: