RESUMO
BACKGROUND/AIMS: Monensin, an Na ionophore, increases intracellular Na ([Na]i). Alteration of [Na]i influences ion transport through the sarcolemmal membrane. So far, the effects of monensin on ventricular myocytes have not been examined in detail. The main objective of this study was to elucidate the mechanism via which monensin-evoked increases in [Na]i affect the membrane potential and currents in ventricular myocytes of guinea pigs. METHODS: Membrane potentials and currents were measured using the whole-cell patch-clamp technique in single myocytes. The concentration of intracellular Ca ([Ca]i) was evaluated by measuring fluorescence intensity of Fluo-4. RESULTS: Monensin (10-5M) shortened the action potential duration (APD) and reduced the amplitude of the plateau phase. In addition, monensin decreased the sodium current (INa) and shifted the inactivation curve to the hyperpolarized direction. Moreover, it decreased the L-type calcium current (ICa). However, this effect was attenuated by increasing the buffering capacity of [Ca]i. The Na-Ca exchange current (INa-Ca) was activated particularly in the reverse mode. Na-K pump current (INa-K) was also activated. Notably, the inward rectifying K current (IK1) was not affected, and the change in the delayed outward K current (IK) was not evident. CONCLUSION: These results suggest that the monensin-induced shortened APD and reduced amplitude of the plateau phase are primarily due to the decrease in the ICa, the activation of the reverse mode of INa-Ca, and the increased INa-K, and second due to the decreased INa. The IK and the IK1 may not be associated with the abovementioned changes induced by monensin. The elevation of [Na]i can exert multiple influences on electrophysiological phenomena in cardiac myocytes.
Assuntos
Monensin/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Ionóforos de Sódio/farmacologia , Sódio/metabolismo , Potenciais de Ação/efeitos dos fármacos , Animais , Cálcio/metabolismo , Cardiotônicos/farmacologia , Cátions/metabolismo , Células Cultivadas , Técnicas Eletrofisiológicas Cardíacas , Cobaias , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Masculino , Potenciais da Membrana/efeitos dos fármacos , Microscopia de Fluorescência , Miócitos Cardíacos/metabolismo , Ouabaína/farmacologia , Técnicas de Patch-Clamp , Potássio/metabolismo , Trocador de Sódio e Cálcio/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/efeitos dos fármacosRESUMO
This study was designed to obtain information on the residual influence of dietary monensin on ruminant fermentation, methanogenesis and bacterial population. Three ruminally cannulated crossbreed heifers (14 months old, 363 ± 11 kg) were fed Italian ryegrass straw and concentrate supplemented with monensin for 21 days before sampling. Rumen fluid samples were collected for analysis of short chain fatty acid (SCFA) profiles, monensin concentration, methanogens and rumen bacterial density. Post-feeding rumen fluid was also collected to determine in vitro gas production. Monensin was eliminated from the rumen fluid within 3 days. The composition of SCFA varied after elimination of monensin, while total production of SCFA was 1.78 times higher than on the first day. Methane production increased 7 days after monensin administration ceased, whereas hydrogen production decreased. The methanogens and rumen bacterial copy numbers were unaffected by the withdrawal of monensin.