The effects of gadolinium, a stretch-sensitive channel blocker, on diaphragm muscle

Abstract

The effects of gadolinium, a stretch-sensitive channel blocker, on diaphragm muscle. C. Coirault, M-P. Sauviat, D. Chemla, J-C. Pourny, Y. Lecarpentier #ERS Journals Ltd 1999. ABSTRACT: 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 (Gd 3+ ), 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 mmol 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), Ca 2+ -free medium (n=6) or after 5 mmol nifedipine (n=8). Gd 3+ reduced active tension measured over a range of initial muscle lengths in a concentration-dependent manner (10 and 50 mmol). In isolated fibres, mechanical stretch generated a membrane current that was sensitive to Gd 3+ . In muscles, lowering [Na + ] e mimicked the effects of Gd 3+ , while no change in the length-tension relationship was observed in Ca 2+ -free medium or after nifedipine. Drugs which increase cAMP prevented the effects of Gd 3+ 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.

Involvement of the Neurokinin-2 Receptor in Airway Smooth Muscle Stretch-Activated Contractions Assessed in Perfused Intact Bovine Bronchial Segments

“…To investigate whether stretch-activated cation channels are involved in R stretch,30 , we used a mechanosensitive cation channel blocker, Gd 3ϩ (Coirault et al, 1999). Control responses were established upon pretreatment with 10…”

Fate of tenogenic differentiation potential of human bone marrow stromal cells by uniaxial stretching affected by stretch-activated calcium channel agonist gadolinium

“…A study of Coirault et al [38] demonstrated that effects of Gd 3+ were not due to inhibition of voltage-gated Ca 2+ channels. A selective stretch-activated channel blocker would allow the relative contribution of stretch- and voltage-activated channels to tension development to be quantified more precisely.…”

“…At present, there have been no such blocker available that has a similar function to gadolinium, and as such, gadolinium is presently the only prescribed blocker of stretch-activated channels [39–41]. In previous studies, cation channels are blocked using Gd 3+ , in concentrations of 10–100 μM, depends on cell types [38, 42–45]. Incubation of cells with high concentrations of Gd 3+ blocks electrical stimulation-induced concentration of intracellular calcium increases, as well as inhibiting the influx and efflux of calcium [40].…”

Molecular neurochemistry of the lanthanides

“…This finding may help to introduce a new pharmacological tool to distinguish between heat signaling of TRPV2 and the similar capsaicin‐receptor, TRPV1, which is strongly sensitized by lanthanides (Leffler, Linte, Nau, Reeh, & Babes, ). Of interest, Gd 3+ strongly blocks stretch‐sensitive ion channels (SACs) in the sarcolemma of skeletal muscle fibers (Coirault, Sauviat, Chemla, Pourny, & Lecarpentier, ). Both Gd 3+ and La 3+ were also potent inhibitors of the lysoplasmenylcholine‐induced current and equally delayed the onset of myocyte contractions in the rabbit heart, but surprisingly Gd 3+ sensitive SACs were not blocked by this ion (Caldwell & Baumgarten, ).…”

“…Of interest, Gd 3+ strongly blocks stretch-sensitive ion channels (SACs) in the sarcolemma of skeletal muscle fibers (Coirault, Sauviat, Chemla, Pourny, & Lecarpentier, 1999). Both Gd 3+ and La 3+ were also potent inhibitors of the lysoplasmenylcholine-induced current and equally delayed the onset of myocyte contractions in the rabbit heart, but surprisingly Gd 3+ sensitive SACs were not blocked by this ion (Caldwell & Baumgarten, 1998).…”