Format

Send to

Choose Destination
Cell Calcium. 2019 May;79:68-74. doi: 10.1016/j.ceca.2019.02.008. Epub 2019 Feb 22.

L-type calcium channel modulates mechanosensitivity of the cardiomyocyte cell line H9c2.

Author information

1
Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan; Department of Physiology, Nagoya University School of Medicine, Nagoya, 466-8550, Japan. Electronic address: takah-k2@okayama-u.ac.jp.
2
Department of Physiology, Nagoya University School of Medicine, Nagoya, 466-8550, Japan.
3
Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan; Department of Cardiology, Qingdao Municipal Hospital, Qingdao, 266001, China.
4
Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
5
Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan; Department of Pathophysiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, 150081, China.
6
Department of Physiology, Nagoya University School of Medicine, Nagoya, 466-8550, Japan; Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.

Abstract

The application of mechanical stimuli to cells often induce increases in intracellular calcium, affecting the regulation of a variety of cell functions. Although the mechanism of mechanotransduction-induced calcium increases has not been fully resolved, the involvement of mechanosensitive ion channels in the plasma membrane and the endoplasmic reticulum has been reported. Here, we demonstrate that voltage-gated L-type calcium channels play a critical role in the mechanosensitive calcium response in H9c2 rat cardiomyocytes. The intracellular calcium level in H9c2 cells increased in a reproducible dose-dependent manner in response to uniaxial stretching. The stretch-activated calcium response (SICR) completely disappeared in calcium-free medium, whereas thapsigargin and cyclopiazonic acid, inhibitors of sarcoendoplasmic reticulum calcium ATPase, partially reduced the SICR. These findings suggest that both calcium influx across the cell membrane and calcium release from the sarcoendoplasmic reticulum are involved in the SICR. Nifedipine, diltiazem, and verapamil, inhibitors of L-type calcium channels, reduced the SICR in a dose-dependent manner. Furthermore, small interfering RNA against the L-type calcium channel α1c subunit diminished the SICR dramatically. Nifedipine also diminished the mechanosensitivity of Langendorff-perfused rat heart. These results suggest that the SICR in H9c2 cardiomyocytes involves the activation of L-type calcium channels and subsequent calcium release from the sarcoendoplasmic reticulum.

KEYWORDS:

Calcium-induced calcium release; Cardiomyocyte; Mechanosensitivity; Voltage-gated calcium channel

PMID:
30836292
DOI:
10.1016/j.ceca.2019.02.008
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center