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.

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