Crecimiento

En la presente clase se toma como excusa el estudio del crecimiento de una persona, desde su concepción hasta la etapa adulta, para abordar todas las estructuras, órganos y sistemas que deben funcionar correctamente para permitir un buen crecimiento.Facultad de Ciencias Médica

Angiotensin II inhibits the electrogenic Na+/HCO3- cotransport of cat cardiac myocytes

The Na+/HCO3- cotransporter (NBC) plays an important role in intracellular pH (pHi) regulation in the heart. In the myocardium co-exist the electrogenic (eNBC) and electroneutral (nNBC) isoforms of NBC. We have recently reported that angiotensin II (Ang II) stimulated total NBC activity during the recovery from intracellular acidosis through a reactive oxygen species (ROS) and ERK-dependent pathway. In the present work we focus our attention on eNBC. In order to study the activity of the eNBC in isolation, we induced a membrane potential depolarization by increasing extracellular K+ [K+]o from 4.5 to 45mM (K+ pulse). This experimental protocol enhanced eNBC driving force leading to intracellular alkalization (0.19±0.008, n=6; data expressed as an increase of pHi units after 14min of applying the K+ pulse). This alkalization was completely abrogated by the NBC blocker S0859 (-0.004±0.016*, n=5; * indicates p<0.05 vs control) but not by the Na+/H+ exchanger blocker HOE642 (0.185±0.04, n=4), indicating that we are exclusively measuring eNBC. The K+ pulse induced alkalization was canceled by 100nM Ang II (-0.008±0.018*; n=5). This inhibitory effect was prevented when the myocytes were incubated with losartan (AT1 receptor blocker, 0.18±0.02; n=4) or SB202190 (p38 MAP kinase inhibitor, 0.25±0.06; n=5). Neither chelerythrine (PKC inhibitor, -0.06±0.04*; n=4), nor U0126 (ERK inhibitor, -0.07±0.04*; n=4) nor MPG (ROS scavenger, -0.02±0.05*; n=8) affected the Ang II-induced inhibition of eNBC. The inhibitory action of Ang II on eNBC was corroborated with perforated patch-clamp experiments, since no impact of the current produced by eNBC on action potential repolarization was observed in the presence of Ang II. In conclusion, we propose that Ang II, binding to AT1 receptors, exerts an inhibitory effect on eNBC activity in a p38 kinase-dependent manner. © 2010 Elsevier Ltd.Fil: de Giusti, Verónica Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Orlowski, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Aiello, Ernesto Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentin

Regulation of the cardiac sodium/bicarbonate cotransporter by angiotensin II : Potential Contribution to structural, ionic and electrophysiological myocardial remodelling

The sodium/bicarbonate cotransporter (NBC) is, with the Na+ /H+ exchanger (NHE), an important alkalinizing mechanism that maintains cellular intracellular pH (pHi). In the heart exists at least three isoforms of NBC, one that promotes the co-influx of 1 molecule of Na+ per 1molecule of HCO3- (electroneutral isoform; nNBC) and two others that generates the co-influx of 1 molecule of Na+ per 2 molecules of HCO3- (electrogenic isoforms; eNBC). In addition, the eNBC generates an anionic repolarizing current that modulate the cardiac action potential (CAP), adding to such isoforms the relevance to modulate the electrophysiological function of the heart. Angiotensin II (Ang II) is one of the main hormones that regulate cardiac physiology. The alkalinizing mechanisms (NHE and NBC) are stimulated by Ang II, increasing pHi and intracellular Na+ concentration, which indirectly, due to the stimulation of the Na+/Ca2+ exchanger (NCX) operating in the reverse form, leads to an increase in the intracellular Ca2+ concentration. Interestingly, it has been shown that Ang II exhibits an opposite effect on NBC isoforms: it activates the nNBC and inhibits the eNBC. This inhibition generates a CAP prolongation, which could directly increase the intracellular Ca2+ concentration. The regulation of the intracellular Na+ and Ca2+ concentrations is crucial for the cardiac cellular physiology, but these ions are also involved in the development of cardiac hypertrophy and the damage produced by ischemia-reperfusion, suggesting a potential role of NBC in cardiac diseases.Centro de Investigaciones Cardiovasculare

Echoes of the annual meeting SAFIS-ALACF 2021 : Reflections and Images

In February 2021 with wishful eyes, we started planning our annual reunion of the Argentinean Society of Physiology (SAFIS). The goal ahead was a fully face-to-face meeting in La Plata in October. However, the devil shook his tail and what seemed a declining phase in the Covid-19 pandemic resulted in further outbreak and major lockdown. Under this situation, and without a clear prospective, we decided to switch to a totally virtual meeting, taking advantage of this new tool of communication and learning that we all experienced and have become familiar with during the last 2 years. With no delay, we began planning our SAFIS 2021 virtual meeting with excitement, anxiety and hard work. Our main goal now was to break the stigma of virtuality, that is: long tedious hours in front of the monitor listening to recorded videos without the possibility of a fluid discussion. To achieve this objective, we took the risky decision of having only synchronous sessions with no prerecorded videos. Each symposium or plenary conference would have all the invited speakers together in a zoom session assisted with two chairmen to help with the discussion. These activities would be retransmitted via streaming in real-time for the congress assistants to follow and open the chat rooms for questions. Of course, nothing is sufficient to keep the viewers’ attention if the program isn’t worthy. For this we put together an attractive, innovative and provocative scientific program focused on fostering new knowledge, networking and training, mixed with tablets of more distended talks and short videos to sit back en enjoy. We also concentrated on a program that included internationally as well as locally recognized senior physiologist with a history of cutting-edge research as well as the most promising investigators from early, mid and established investigator levels. In addition, this year, the SAFIS Education Committee organized a workshop on virtual teaching of physiology and for the first time we had a prominent spot in our program for two symposia organized entirely by the Committee of Early Career Investigators. As a hallmark of our annual meeting the highlights were centered in the poster and Award sessions which spotlighted the SAFIS Prize to best work in general physiology, the Camilión de Hurtado Prize to the best study in cardiovascular physiology and the María de los Angeles Costa Prize to the best poster in the area of education.Sociedad Argentina de Fisiologí

Modulation of the cardiac sodium/bicarbonate cotransporter by the renin angiotensin aldosterone system: pathophysiological consequences

The sodium/bicarbonate cotransporter (NBC) is one of the major alkalinizing mechanisms in the cardiomyocytes. It has been demonstrated the existence of at least two functional isoforms, one that promotes the co-influx of 1 molecule of Na+ per 1 molecule of HCO¯3 (electroneutral isoform; NBCn1) and the other one that generates the co-influx of 1 molecule of Na+ per 2 molecules of HCO¯3 (electrogenic isoform; NBCe1). Both isoforms are important to maintain intracellular pH (pHi) and sodium concentration ([Na+]i). In addition, NBCe1 generates an anionic repolarizing current that modulates the action potential duration (APD). The renin-angiotensin-aldosterone system (RAAS) is implicated in the modulation of almost all physiological cardiac functions and is also involved in the development and progression of cardiac diseases. It was reported that angiotensin II (Ang II) exhibits an opposite effect on NBC isoforms: it activates NBCn1 and inhibits NBCe1. The activation of NBCn1 leads to an increase in pHi and [Na+]i, which indirectly, due to the stimulation of reverse mode of the Na+/Ca2+ exchanger (NCX), conduces to an increase in the intracellular Ca2+ concentration. On the other hand, the inhibition of NBCe1 generates an APD prolongation, potentially representing a risk of arrhythmias. In the last years, the potentially altered NBC function in pathological scenarios, as cardiac hypertrophy and ischemia-reperfusion, has raised increasing interest among investigators. This review attempts to draw the attention on the relevant regulation of NBC activity by RAAS, since it modulates pHi and [Na+]i, which are involved in the development of cardiac hypertrophy, the damage produced by ischemia-reperfusion and the generation of arrhythmic events, suggesting a potential role of NBC in cardiac diseases.Facultad de Ciencias MédicasCentro de Investigaciones Cardiovasculare

Generación de anticuerpos inhibitorios de la función del cotransportador sodio/bicarbonato cardíaco : Una posible futura herramienta terapéutica

El cotransportador Na+/HCO3- (NBC) cardíaco es un importante mecanismo alcalinizante encargado de regular el pH intracelular (pHi) en las células cardíacas. En el corazón se han identificado al menos 3 isoformas del NBC: 1 electroneutra (NBC3), con estequiometría 1 Na+ 1 HCO3-, y 2 electrogénicas (NBC1 y NBC4), las cuales introducen 2 moléculas de HCO3- por cada 1 de Na+. Dado que este último mecanismo genera una corriente aniónica repolarizante, su correcto funcionamiento es relevante en el control de la forma y duración del potencial de acción (PA).Centro de Investigaciones Cardiovasculare

Las especies reactivas del oxígeno son las responsables del fenómeno de la escalera negativa en la rata

La relación entre frecuencia de estimulación y fuerza de contracción (RE-F) es un importante mecanismo de regulación de la contractilidad cardíaca. Si un aumento en la frecuencia de estimulación induce un aumento de la fuerza de contracción se considera una RE-F positiva (escalera positiva); por otro lado en una RE-F negativa (escalera negativa) la fuerza de contracción disminuye al aumentar la frecuencia de estimulación; este fenómeno se describe en la rata. Se conoce que las especies reactivas del oxígeno (ROS) son las mediadoras intracelulares del efecto inotrópico positivo inducido por Angiotensina II, Endotelina y Aldosterona. Sin embargo la participación de ROS durante la RE-F no ha sido investigada en su totalidad.Facultad de Ciencias Médica

Las especies reactivas del oxígeno son las responsables del fenómeno de la escalera negativa en la rata

La relación entre frecuencia de estimulación y fuerza de contracción (RE-F) es un importante mecanismo de regulación de la contractilidad cardíaca. Si un aumento en la frecuencia de estimulación induce un aumento de la fuerza de contracción se considera una RE-F positiva (escalera positiva); por otro lado en una RE-F negativa (escalera negativa) la fuerza de contracción disminuye al aumentar la frecuencia de estimulación; este fenómeno se describe en la rata. Se conoce que las especies reactivas del oxígeno (ROS) son las mediadoras intracelulares del efecto inotrópico positivo inducido por Angiotensina II, Endotelina y Aldosterona. Sin embargo la participación de ROS durante la RE-F no ha sido investigada en su totalidad.Facultad de Ciencias Médica

Las especies reactivas del oxígeno son las responsables del fenómeno de la escalera negativa en la rata

La relación entre frecuencia de estimulación y fuerza de contracción (RE-F) es un importante mecanismo de regulación de la contractilidad cardíaca. Si un aumento en la frecuencia de estimulación induce un aumento de la fuerza de contracción se considera una RE-F positiva (escalera positiva); por otro lado en una RE-F negativa (escalera negativa) la fuerza de contracción disminuye al aumentar la frecuencia de estimulación; este fenómeno se describe en la rata. Se conoce que las especies reactivas del oxígeno (ROS) son las mediadoras intracelulares del efecto inotrópico positivo inducido por Angiotensina II, Endotelina y Aldosterona. Sin embargo la participación de ROS durante la RE-F no ha sido investigada en su totalidad.Facultad de Ciencias Médica

Reduced sarcolemmal expression and function of the NBCe1 isoform of the Na+‒HCO¯3 cotransporter in hypertrophied cardiomyocytes of spontaneously hypertensive rats: Role of the renin-angiotensin system

Aims. Electroneutral (NBCn1) and electrogenic (NBCe1) isoforms of the Na+‒HCO¯3 cotransporter (NBC) coexist in the heart. We studied the expression and function of these isoforms in hearts of Wistar and spontaneously hypertensive rats (SHR), elucidating the direct implication of the renin-angiotensin system in the NBC regulation. Methods and results. We used myocytes from Wistar, SHR, losartan-treated SHR (Los-SHR), and Angiotensin II (Ang II)-induced cardiac hypertrophy. We found an overexpression of NBCe1 and NBCn1 proteins in SHR that was prevented in Los-SHR. Hyperkalaemic-induced pHi alkalization was used to study selective activation of NBCe1. Despite the increase in NBCe1 expression, its activity was lower in SHR than in Wistar or Los-SHR. Similar results were found in Ang II-induced hypertrophy. A specific inhibitory antibody against NBCe1 allowed the discrimination between NBCe1 and NBCn1 activity. Whereas in SHR most of the pHi recovery was due to NBCn1 stimulation, in Wistar and Los-SHR the activity of both isoforms was equitable, suggesting that the deteriorated cardiac NBCe1 function observed in SHR is compensated by an enhanced activity of NBCn1. Using the biotin method, we observed greater level of internalized NBCe1 protein in SHR than in the non-hypertophic groups, while with immunofluorescence we localized the protein in endosomes near the nucleus only in SHR. Conclusions. We conclude that Ang II is responsible for the impairment of the NBCe1 in hypertrophied hearts. This is due to retained transporter protein units in early endosomes. Moreover, NBCn1 activity seems to be increased in the hypertrophic myocardium of SHR, compensating impaired function of NBCe1.Facultad de Ciencias MédicasCentro de Investigaciones Cardiovasculare