Estudo da modulação do canal de sodio pela ativação da proteina quinase

AUTOR(ES)
DATA DE PUBLICAÇÃO

1994

RESUMO

Sodium channels are responsible for the generation of cellular electrical activity involved in specific functions, such as cardiac cell contraction for heart beating, or electrical signal transmission performed by nerve cells for the whole body control. Sodium channels are modulated by many cell mechanisms, incIuding phosphorylation(phosphate ion bonding) of the channelprotein by protein kinases. Protein kinaseC, which is activated when intracellulardiacylglicerolconcentrationis increasedby alpha -adrenergic or cholinergic stimulation,is known to be a sodium channel phosforylator. In this work, we have studied the effects of three different protein kinase C activators (diacylglicerols, cis-unsaturated fatty acids and forbol esters) on sodium channel and suggested a biophysical mechanism for modulation by one kind of the protein kinase C activator (the diacylglicerols). We have used two patch clamp techniques for the sodium current recording in mouse neuroblastoma cells (NIE- 115): i) perforated patch clamp for macroscopic sodium currents recording and li) cellattached patch clamp for single channel recording. The results showed that protein kinase C activators have multiple effects on sodium currents. These results suggested that protein kinase C activation modulates the sodium channel by more. than one mechanism. Protein quinase C activation by diacylglicerol decreased the sodium current amplitude and shifted the inactivation curve to more negative voltages. Considering a biophysical model based on state transitions of the sodium channel and the experimental results that confmned the model predictions, we proposed that the mechanism by which the diacylglicerols modulate sodium channel is an increase on the number of sodium channels direct1y inactivating from their resting state. This diacylglicerol effect represents a simple and efficient biophysical mechanism by which protein kinase C activation might modulate sodium channel function and consequent1y, the cell electrical activity

ASSUNTO(S)

sequencia de aminoacidos sodio - efeito fisiologico proleinas

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