Role of inositol 1,4,5-trisphosphate receptor type 1 in ATP-induced nuclear Ca2+ signal and hypertrophy in atrial myocytes

• Published in: Biochemical and biophysical research communications Vol. 503; no. 4; pp. 2998 - 3002
• Main Authors: Kim, Joon-Chul, Son, Min-Jeong, Le, Qui Anh, Woo, Sun-Hee
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.09.2018
• Subjects: 60 APPLIED LIFE SCIENCES; adenosine triphosphate; agonists; ATP; Atrial myocytes; calcium; CALCIUM IONS; calcium signaling; ENDOTHELINS; HEART; Hypertrophy; image analysis; INOSITOL; IP3R1; MUSCLES; myocytes; Nuclear Ca2; phenylephrine; IP3R1; IP3R2; F; RyR; ROI; Atrial myocytes; SDS-PAGE; ET-1; Tp,90; PE; NE; KD; Nuclear Ca2; ATP; RFP; WT; Hypertrophy; SR
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2018.08.084

Inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) is expressed in atrial muscle, but not in ventricle, and they are abundant in the perinucleus. We investigated the role of IP3R1 in the regulations of local Ca2+ signal and cell size in HL-1 atrial myocytes under stimulation by IP3-generating chemical messenger, ATP. Assessment of nuclear and cytosolic Ca2+ signal using confocal Ca2+ imaging revealed that IP3 generation by ATP (1 mM) induced monophasic nuclear Ca2+ increase, followed by cytosolic Ca2+ oscillation. Genetic knock-down (KD) of IP3R1 eliminated the monophasic nuclear Ca2+ signal and slowed the cytosolic Ca2+ oscillation upon ATP exposure. Prolonged application of ATP as well as other known hypertrophic agonists (endothelin-1 and phenylephrine) increased cell size in wild-type cells, but not in IP3R1 KD cells. Our data indicate that IP3R1 mediates sustained elevation in nuclear Ca2+ level and facilitates cytosolic Ca2+ oscillation upon external ATP increase, and further suggests possible role of nuclear IP3R1 in atrial hypertrophy. •IP3 receptor type 1 (IP3R1) are expressed in atrial cell perinucleus.•IP3R1 mediates ATP-induced sustained nuclear Ca2+ increase in HL-1 atrial cells.•IP3R1 contributes to higher sensitivity of nuclear release sites upon IP3 increase.•Larger Ca2+ content in perinuclear store of atrial cells involves IP3R1.•IP3R1 signaling may play a role in ATP-induced atrial cell hypertrophy.