The effects of gadolinium, a stretch-sensitive channel blocker, on diaphragm muscle.
Stretch-activated channels (SAC) have been identified in many cell types including striated muscles. In diaphragm muscle, the influence of SAC on the length-active tension relationship remains unknown. Patch clamp experiments were performed on single fibres (n = 10). In isolated diaphragm muscle from adult hamsters, the effects of gadolinium (Gd3+), the most potent inhibitor of SAC blocker, on tension response to stretch at baseline were studied (n = 10), after pretreatment of the muscle with 1 nmol isoproterenol (n = 10), 0.5 micromol forskolin (n = 6), or 0.1 mmol dibutyryl cyclic adenosine monophosphate (cAMP) (n = 10). Results were compared to those obtained in low [Na+]e (n = 10), Ca2+-free medium (n = 6) or after 5 micromol nifedipine (n = 8). Gd3+ reduced active tension measured over a range of initial muscle lengths in a concentration-dependent manner (10 and 50 micromol). In isolated fibres, mechanical stretch generated a membrane current that was sensitive to Gd3+. In muscles, lowering [Na+]e mimicked the effects of Gd3+, while no change in the length-tension relationship was observed in Ca2+-free medium or after nifedipine. Drugs which increase cAMP prevented the effects of Gd3+ on active tension. In the diaphragm, gadolinium-sensitive channels are activated during physiological changes in length and influence tension development. Moreover, cyclic adenosine monophosphate content modulates the effects of gadolinium on stretch-activated channels.
Coirault
C
C
U 451 INSERM-Laboratoire d'Optique Appliquée-ENSTA Ecole Polytechnique, Palaiseau, France.
Sauviat
M P
MP
Chemla
D
D
Pourny
J C
JC
Lecarpentier
Y
Y
D000200:Action Potentials; D000249:Adenosine Monophosphate / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D046508:Culture Techniques; D003964:Diaphragm / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005071:Evoked Potentials; D005682:Gadolinium / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects*; D007537:Isometric Contraction / Q000187:drug effects* / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008647:Mesocricetus; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques
D007473:Ion Channels; D005576:Colforsin; D000249:Adenosine Monophosphate; D005682:Gadolinium; D000262:Adenylyl Cyclases; D009543:Nifedipine; D007545:Isoproterenol