OU-MRU Vol.4 Dec 2014

Okayama University Medical Research Updates （OU-MRU）
Source: Okayama University (JAPAN), Center for Public Information
For immediate release:
Okayama University research: cardiac mechanosensitive integrator(Okayama, 22 December 2014) Researchers at Okayama University Graduate School ofMedicine and co-workers across Japan have uncovered the crucial role played by aparticular protein (TRPV2) in maintaining a healthy heart

The heart is a dynamic, finely-tuned mechanical structure which must continually respondto fluctuations in blood flow in the body. Exercise and pregnancy can strengthen the heart,
requiring it to improve cardiac muscle power and pumping ability. Prolonged bed rest andlack of exercise leads to ‘cardiac atrophy’ – the wasting away of muscles, reducing theheart’s ability to pump blood effectively. However, despite the importance of the heart’s
responses to mechanical forces, the mechanisms behind healthy cardiac mechanics are notclear.
Now, Yuki Katanosaka and co-workers at Okayama University, together with scientists
across Japan, have uncovered the role of a particular protein called TRPV2 in maintaining ahealthy, functioning heart1.
TRPV2 is one of a group of proteins known to act as sensors for flow changes and tension incells. TRPV2 is highly localised in microscopic elements of cardiac muscles known as‘intercalated discs’, which are responsible for synching heart-muscle contractions. Theinteraction between intercalated discs and myocytes – the muscle cells which create theelectrical impulses that control heart rate - drives the healthy expansion and contraction ofthe heart.
Katanosaka and her team generated temporally controlled cardiac-specific TRPV2-deficient
mice in order to clarify the role of the protein. They found that, within four days ofeliminating TRPV2, heart function declined rapidly – coupling between myocytes andintercalated discs was severely disrupted, and the discs became disordered. After nine days,
the myocytes displayed problems handling calcium ions, leading to poor cardiac muscle
contraction.
The researchers also discovered that TRPV2-deficient neonatal myocytes did not form
mature intercalated discs. They believe TRPV2 may have a crucial role co-ordinating thetransmission of forces through cardiac muscle.

OKAYAMA University
1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530 Japan© OKAYAMA University

OU-MRU Vol.4 Dec 2014

Background
The mechanical structures in the heart must respond quickly to changes in blood flow andstress in order to maintain healthy, effective cardiac function. Both exercise and pregnancy
require the heart to work harder; the mass of the heart increases, heart wall thickness
increases and the ability of the heart to pump blood around the body improves. Prolonged
bed rest, lack of exercise, and more unusual situations such as weightlessness in zero-gravity,
can also lead to thickening of the heart wall, but the cardiac muscles are weakened, and theblood-pumping action is considerably reduced.
The regular expansion and contraction of the heart is controlled by two key features of theheart muscle – muscle cells known as myocytes, and microscopic cell-to-cell junctions
unique to cardiac muscles known as ‘intercalated discs’. These discs are coupled with themyocytes at their termini and together form a single functioning unit. Cardiac myocytes
create the electrical impulses that control heart rate, and the discs help synch thecontraction of cardiac muscle tissue. If the coupling mechanism between these two features
is disrupted, the heart fails to function correctly and no longer pumps blood effectively
around the body.
Yuki Katanosaka and her team at Okayama University have made a crucial link between theprotein TRPV2 and the healthy co-ordination of mechanical forces within heart muscle
tissue. The contraction of the heart and subsequent pumping of blood around the body
appears to be largely controlled by the presence of TRPV2 in intercalated discs within themuscles. Without TRPV2, heart structure and function rapidly declines.

Reference
Yuki Katanosaka, Keiichiro Iwasaki, Yoshihiro Ujihara, Satomi Takatsu, Koki Nishitsuji, MotoiKanagawa, Atsushi Sudo, Tatsushi Toda, Kimiaki Katanosaka, Satoshi Mohri, & Keiji Naruse.
TRPV2 is critical for the maintenance of cardiac structure and function in mice. Nature
Communications (2014)
Abstract URL:
http://www.nature.com/ncomms/2014/140529/ncomms4932/full/ncomms4932.html
DOI: 10.1038/ncomms4932

OKAYAMA University
1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530 Japan© OKAYAMA University

OU-MRU Vol.4 Dec 2014Figure caption: Researchers at Okayama University have uncovered the role of protein
TRPV2 in maintaining a healthy, functioning heart in mice models. The protein works tomaintain links between muscle cells and cell-to-cell junctions known as intercalated discs,
leading to effective expansion and contraction of the heart muscle.

Correspondence toAssistant Professor Yuki Katanosaka, Ph.D.
Department of Cardiovascular Physiology, Graduate
School of Medicine, Dentistry and PharmaceuticalSciences, Okayama University, Shikata-cho 2-5-1,Okayama city, Okayama 700-8558, Japan
E-mail: ytanigu@md.okayama-u.ac.jp

Further information
Okayama University
1-1-1 Tsushima-naka , Kita-ku , Okayama 700-8530, Japan
Planning and Public Information Division, Okayama University
E-mail: www-adm@adm.okayama-u.ac.jp
Website: http://www.okayama-u.ac.jp/index_e.html
Okayama Univ. e-Bulletin：http://www.okayama-u.ac.jp/user/kouhou/ebulletin/

OKAYAMA University
1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530 Japan© OKAYAMA University

OU-MRU Vol.4 Dec 2014

Okayama University Medical Research Updates （OU-MRU）
Vol.1：Innovative non-invasive ‘liquid biopsy’ method to capture circulating tumor cells
from blood samples for genetic testing
Vol.2：Ensuring a cool recovery from cardiac arrest
Vol.3：Organ regeneration research leaps forward

About Okayama UniversityOkayama University is one of the largest
comprehensive universities in Japan withroots going back to the Medical Training
Place sponsored by the Lord of Okayama
and established in 1870. Now with 1,300
faculty and 14,000 students, the University
offers courses in specialties ranging frommedicine and pharmacy to humanities
and physical sciences. Okayama
University is located in the heart of Japan
approximately 3 hours west of Tokyo byShinkansen.

OKAYAMA University
1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530 Japan© OKAYAMA University