Why the study?
Do midazolam and diazepam decrease Ca2+ transients and beating rate in cultured foetal mouse cardiac myocytes?
Do midazolam and diazepam decrease Ca2+ transients and beating rate in cultured foetal mouse cardiac myocytes?
Midazolam and diazepam act as direct cardiac depressants by decreasing Ca2+ transients and beating rate via L-type Ca2+ channels in foetal mouse ventricular myocytes.
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Should not change benzodiazepine use in humans; leaves open translation of L-type Ca channel effects from fetal mouse myocytes to clinical practice.
We have investigated the effects of midazolam and diazepam on intracellular calcium (Ca2+) handling in foetal mouse ventricular myocytes using the Ca(2+)-sensitive fluorescent indicator, indo-1. We also investigated separately whether flumazenil or the L-type Ca2+ channel agonist, Bay K8644, antagonized these myocardial depressive effects. Midazolam and diazepam decreased the Ca2+ transient and beating rate in a concentration-dependent manner, and these decreases were prevented by Bay K8644. Flumazenil did not antagonize the myocardial depressive effects. In myocytes whose sarcoplasmic reticulum was inhibited by ryanodine, midazolam and diazepam had the same potent cardiodepressive effects. Midazolam and diazepam are direct cardiac depressants, which decrease the Ca2+ transient and beating rate, and the L-type Ca2+ channel is important in the negative inotropism and chronotropism caused by these drugs.
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Nonaka et al. (1997) studied this question.
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