© 2000 American Heart Association, Inc.
Cellular Biology |
Pulsatile Stretch Remodels Cell-to-Cell Communication in Cultured Myocytes
From the Department of Physiology, University of Bern, Switzerland, and the Center for Cardiovascular Research, Washington University, St. Louis, Mo.
Correspondence to André G. Kléber, MD, Department of Physiology, University of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland. E-mail kleber{at}pyl.unibe.ch
Abstract—Mechanical stretch is
thought to play an important role in remodeling atrial and
ventricular myocardium and may produce
substrates that promote arrhythmogenesis. In the present work,
neonatal rat ventricular myocytes were cultured for 4 days
as confluent monolayers on thin silicone membranes and then subjected
to linear pulsatile stretch for up to 6 hours. Action potential
upstrokes and propagation velocity (
) were measured with multisite
optical recording of transmembrane voltage of the cells stained
with the voltage-sensitive dye RH237. Expression of the gap junction
protein connexin43 (Cx43) and the fascia adherens junction protein
N-cadherin was measured immunohistochemically in the same preparations.
Pulsatile stretch caused dramatic upregulation of intercellular
junction proteins after only 1 hour and a further increase after 6
hours (Cx43 signal increased from 0.73 to 1.86 and 2.02% cell area,
and N-cadherin signal increased from 1.21 to 2.11 and 2.74% cell area
after 1 and 6 hours, respectively). This was paralleled by an
increase in from 27 to 35 cm/s after 1 hour and 37 cm/s after 6
hours. No significant change in the upstroke velocity of the action
potential or cell size was observed. Increased and protein
expression were not reversible after 24 hours of relaxation.
Nonpulsatile (static) stretch produced qualitatively similar but
significantly smaller changes than pulsatile stretch. Thus, pulsatile
linear stretch in vitro causes marked upregulation of proteins that
form electrical and mechanical junctions, as well as a concomitant
increase in propagation velocity. These changes may contribute to
arrhythmogenesis in myocardium exposed to acute
stretch.
Key Words: remodeling • stretch • connexin43 • conduction velocity
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