EFECTO DEL REMODELADO ELÉCTRICO AURICULAR EN UN MODELO TRIDIMENSIONAL DE AURÍCULA HUMANA

Las arritmias cardíacas más frecuentes en humanos tienen origen auricular. El modelado de la actividad auricular se ha convertido en una importante herramienta en el análisis de arritmias como la fibrilación auricular. Estudios experimentales han demostrado que la fibrilación auricular tiende a perpetuarse, generando cambios electrofisiológicos denominados remodelado auricular. En este trabajo se presenta un modelo tridimensional geométricamente realista de la aurícula humana, al cual se le incorporan: anisotropía, dirección de las fibras y heterogeneidad en la conductividad. En un modelo del potencial de acción acoplado al modelo tridimensional, se estudió el efecto del remodelado auricular sobre el potencial de acción y su propagación teniendo en cuenta sus efectos sobre las corrientes iónicas. El modelo reprodujo el comportamiento de la actividad eléctrica en toda la superficie auricular. El remodelado redujo la duración del potencial de acción, el periodo refractario efectivo y la velocidad de conducción. Los resultados sugieren que en el modelo tridimensional desarrollado, es posible simular la actividad eléctrica auricular en condiciones fisiológicas y con remodelado eléctrico auricular.

The most common cardiac arrhythmias in humans originate in the atrium. Modelling of the atrial activity has become an important tool to analyze arrhythmias such as atrial fibrillation. Experimental studies have shown that atrial fibrillation tends to be perpetual, generating electrophysiological changes called atrial remodeling. In this study we present a geometrically realistic three-dimensional (3D) model of human atrium, which incorporates anisotropy, direction of the fibers and conductive heterogeneity. The effects of remodeling on the ionic currents were applied to an action potential model coupled to the 3D model. The effects of remodeling on the action potential and its propagation were studied the model reproduced the electrical activity behavior across the atrial surface. Remodelling induced a reduction in the action potential duration, the effective refractory period and the conduction velocity. Our results suggest that in the developed 3D model of human atrium is possible to simulate the atrial electrical activity under physiological conditions and with atrial electrical remodeling.

El plomo inhibe la corriente activada por protones (ASIC) en las neuronas de los ganglios dorsales / Lead inhibits proton gated currents (ASIC) in dorsal root ganglion neurons

Antecedentes. Los canales iónicos ASIC (del inglés Acid Sensing Ion Channel) son canales iónicos activados por reducciones transitorias en el pH extracelular. Pese a no conocerse con exactitud su mecanismo, la activación ocurre por medio de la unión de protones al dominio extracelular del canal y es modulada por iones calcio y zinc. Objetivo. El hecho de que los cationes divalentes modifiquen el funcionamiento del canal nos llevó a preguntar si el plomo, otro catión divalente, sería capaz de alterar el funcionamiento de los ASIC. Métodos y resultados. Mediante el uso de la técnica de fijación de voltaje en configuración de célula completa en las neuronas de los ganglios de la raíz dorsal de la rata, encontramos que el plomo inhibe la corriente ASIC en forma dependiente de la concentración. Conclusiones. Estos resultados contribuyen a definir los mecanismos de activación de los canales ASIC y a explicar algunos de los mecanismos tóxicos del plomo en el organismo.

BACKGROUND: Acid sensing ion channels (ASIC) are ionic channels activated by transient pH reductions in the ext raceilularenvi ronment. Although the activation mechanism is not fully elucidated, it is clear that the channel is activated by proton binding to its extraceilular domain, a process that is modulated by calcium and zinc. OBJECTIVE: The fact that divalent cations are able to modify ASIC operation, lead us to consider if lead, anotherdivalent cation and widely distributed neurotoxicant, is also capable to affect ASIC function. METHODS: For this purpose, we recordedASiC currents in rat dorsal root ganglion neurons using the whole cell patch-clamp technique. RESULTS: The results indicated that lead inhibits ASIC currents in a concentration -dependent fashion. CONCLUSIONS: These results contribute to the understanding of the activation mechanism of ASIC and to explain some of the toxic mechanisms of lead in the organism.

Characterization of Acetylcholine-induced Currents in Male Rat Pelvic Ganglion Neurons

The pelvic ganglia provide autonomic innervations to the various urogenital organs, such as the urinary bladder, prostate, and penis. It is well established that both sympathetic and parasympathetic synaptic transmissions in autonomic ganglia are mediated mainly by acetylcholine (ACh). Until now, however, the properties of ACh-induced currents and its receptors in pelvic ganglia have not clearly been elucidated. In the present study, biophysical characteristics and molecular nature of nicotinic acetylcholine receptors (nAChRs) were studied in sympathetic and parasympathetic major pelvic ganglion (MPG) neurons. MPG neurons isolated from male rat were enzymatically dissociated, and ionic currents were recorded by using the whole cell variant patch clamp technique. Total RNA from MPG neuron was prepared, and RT-PCR analysis was performed with specific primers for subunits of nAChRs. ACh dose-dependently elicited fast inward currents in both sympathetic and parasympathetic MPG neurons (EC50; 41.4microliterM and 64.0microliterM, respectively). ACh-induced currents showed a strong inward rectification with a reversal potential near 0 mV in current-voltage relationship. Pharmacologically, mecamylamine as a selective antagonist for alpha3beta4 nAChR potently inhibited the ACh-induced currents in sympathetic and parasympathetic neurons (IC50; 0.53micrometer and 0.22micrometer, respectively). Conversely, alpha- bungarotoxin, alpha-methyllycaconitine, and dihydro-beta-erythroidine, which are known as potent and sensitive blockers for alpha7 or alpha4beta2 nAChRs, below micromolar concentrations showed negligible effect. RT-PCR analysis revealed that alpha3 and beta4 subunits were predominantly expressed in MPG neurons. We suggest that MPG neurons have nAChRs containing alpha3 and beta4 subunits, and that their activation induces fast inward currents, possibly mediating the excitatory synaptic transmission in pelvic autonomic ganglia.