Roles of Cl- channels and Ca2+ mobilization in stretch-induced increase of SA node pacemaker activity.
Ionic mechanisms underlying the enhancement of cardiac pacemaking activity by mechanical stretch were investigated in the isolated rabbit sinoatrial (SA) node. A 5-s stretch of 0.2-2.0 g was applied to small tissue strips (1.5 mm x 3.0 mm) of the SA node using a mechanical stimulator. Spontaneous excitation cycle length (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 microM) or glibenclamide (1 microM) did not affect the force-response relationship. The positive chronotropic response to mechanical stretch > 0.5 g was reduced significantly by treatment with 4,4'-dinitrostilbene-2,2'-disulfonic acid (5mM), 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (1 mM), or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (50 microM). The positive chronotropic response was also reduced in a low-Ca2+ (0.36 mM) medium and by bath application of ryanodine (0.1 microM) or thapsigargin (2 microM). These findings suggest the possible involvement of mechanosensitive Cl- channels and intracellular Ca2+ mobilization in the stretch-induced enhancement of pacemaking activity in the mammalian SA node, although other conceivable mechanisms cannot be ruled out.
Arai
A
A
Department of Circulation, Research Institute of Environmental Medicine, Nagoya University, Japan.
Kodama
I
I
Toyama
J
J
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D002909:Chronobiology Phenomena; D003470:Culture Media / Q000378:metabolism; D005260:Female; D005682:Gadolinium / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010812:Physical Stimulation; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D012849:Sinoatrial Node / Q000502:physiology*; D013267:Stilbenes / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018118:Chloride Channels; D003470:Culture Media; D013267:Stilbenes; D005682:Gadolinium; D009543:Nifedipine; D002118:Calcium