Membrane potential of rat ventricular myocytes responds to axial stretch in phase, amplitude and speed-dependent manners.
OBJECTIVE
To elucidate the interdependence between the mechanical state of the myocardium and its electrical activity, previous studies have been performed at the cellular level. However, the information to date has been limited by the technical difficulties associated with stretching single myocytes.


METHODS
We solved this problem by combining two techniques, namely a carbon fiber technique for stretching rat myocytes with wide ranges of amplitude and speed, and ratiometric measurement of a fluorescent indicator (di8-ANEPPS) for evaluating the membrane potential in the non-contact mode.


RESULTS
During systole, stretching caused depolarization that prolonged the action potential duration without affecting the peak amplitude, but the effect was only significant in the late phase. Application of a stretch to quiescent myocytes depolarized the membrane potential in amplitude- and speed-dependent manners, but the response was suppressed by cytochalasin D treatment, suggesting participation of the cytoskeleton in the mechanotransduction mechanism. Finally, ion replacement experiments revealed that although Na+ was the dominant charge carrier for large amplitude stretches, Ca2+ permeation was involved in small amplitude stretches, suggesting amplitude-dependent ion selectivity.


CONCLUSIONS
Application of axial stretching to rat ventricular myocytes changed the membrane potential in phase-, amplitude- and speed-dependent manners. Amplitude may also modulate the ion selectivity of stretch-activated channels.
Nishimura
Satoshi
S
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Japan.
Kawai
Yasuo
Y
Nakajima
Toshiaki
T
Hosoya
Yumiko
Y
Fujita
Hideo
H
Katoh
Masayoshi
M
Yamashita
Hiroshi
H
Nagai
Ryozo
R
Sugiura
Seiryo
S
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D005260:Female; D005456:Fluorescent Dyes; D006352:Heart Ventricles; D066298:In Vitro Techniques; D040542:Mechanotransduction, Cellular; D008564:Membrane Potentials / Q000502:physiology; D008856:Microscopy, Fluorescence; D032383:Myocytes, Cardiac / Q000502:physiology* / Q000648:ultrastructure; D011726:Pyridinium Compounds; D051381:Rats; D017208:Rats, Wistar; D012518:Sarcomeres / Q000648:ultrastructure; D012964:Sodium / Q000378:metabolism
C089669:1-(3-sulfonatopropyl)-4-(beta-(2-(di-n-octylamino)-6-naphthyl)vinyl)pyridinium betaine; D005456:Fluorescent Dyes; D011726:Pyridinium Compounds; D015638:Cytochalasin D; D012964:Sodium; D002118:Calcium