Roles of cl- channels and ca2+ mobilization in stretch-induced
increase of sa node pacemaker activity .
Arai, Akiko, Itsuo Kodama, and Junji Toyama.
Departments of Circulation and Humoral Regulation, Research
Institute of Environmental Medicine, Nagoya University, Nagoya,
Japan
APStracts 2:0455H, 1995.
Ionic mechanisms underlying the enhancement of cardiac pacemaking
activity by mechanical stretch were investigated in the isolated
rabbit sinoatrial (SA) node. A 5-sec stretch of 0.2-2.0 g was applied
to small tissue strips (1.5 x 3.0 mm) of the SA node using a
mechanical stimulator. Cycle length of spontaneous excitation (SPCL)
was monitored by recording endocardial surface potential through
modified bipolar electrodes with high-gain amplification. Influence
of neurotransmitters released from nerve terminals was eliminated by
atropine and propranolol. A stretch >0.2 g caused a significant
shortening of SPCL; there was a positive correlation between the
force and the maximum shortening of SPCL. Treatment of the
preparation with gadolinium (10 [mu]M) or glibenclamide (1 [mu]M) did
not affect the force-response relationship. The positive chronotropic
response to the mechanical stretch >0.5 g was reduced
significantly by treatment with DNDS (5 mM), SITS (1 mM), or DIDS (50
[mu]M). The positive chronotropic response was also reduced in a low
Ca2+ (0.36 mM) medium, and by bath application of ryanodine (0.1
[mu]M) or thapsigargin (2 [mu]M). These findings suggest the
posssible involvement of mechanosensitive Cl- channels and
intracellular Ca2+ mobilization in the stretch-induced enhancement of
pacemaking activity in the mammalian SA node, though other
conceivable mechanisms cannot be ruled out.
Received 23 August 1995; accepted in final form 22 September
1995.
APS Manuscript Number H241-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95