Thèse de doctorat en Aspects moléculaires et cellulaires de la biologie
Soutenue en 2006
Recent studies, on cardiac tissue at the ventricular level, showed in pathological conditions the expression of a calcium-activated nonselective cationic channel (NSCCa) supposed to be implicated in the genesis of arrhythmias. The aim of the present study was to search for this current on other cardiac levels: atria and sino-atrial nodes. Using the inside-out configuration of the patch-clamp technique, we showed the presence, on human atrial cardiomyocytes and mouse SAN cells, of a nonselective cationic current, permeable to monovalents cations but impermeable to divalents cations and anions. The current/voltage relationship is linear with a unitary conductance close to 20 pS. This current is activated by rise of intracellular calcium and membrane depolarization but inhibited by internal ATP. It is blocked by flufenamic acid and glibenclamide. This current probably corresponds to the new cloned protein TRPM4, which shares the same electrophysiological properties. We detected its mRNA transcript on human atrium and mouse SAN tissues and its protein on mouse SAN tissue. If the physiological impact of this channel is unclear, it could be implicated on arrhythmias genesis during ischemia. As the calcium/ATP ratio is increased and then is in favour of its activation. Also, we described at the unitary level on human atrial cardiomyocytes, a new chloride current activated by cell swelling so called ICl. Swell. It could be implicated in the regulatory volume decrease observed during atrial dilatation.
Functional and molecular characterization of a calcium-activated nonselective cationic current on mammalians sino-atrial node and atrial cells
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