Functional coupling between BKCa and P2X channels in human vascular smooth muscle cells

ENRIQUE, NICOLÁS; MARTÍN, PEDRO; MONCADA, MELISA; ASUAJE, AGUSTÍN; MILESI, MARIA VERÓNICA

Rio de Janeiro

Congreso; 38th IUPS Congress (International Union of Physiology Sciences); 2017

IUPS (International Union of Physiology Sciences)

Human vascular smooth muscle cells (SMC) exposed to extracellular ATP (ATPe) evoked a transient inward ionic current, carried by Na+ and Ca2+, characterized by a fast activation followed by a peak current decrease toward the baseline value, typical of desensitization process of P2X purinergic receptors. Among the different roles this Ca2+ influx could have on the SMCs physiology, we focus on its possible functional coupling with the large conductance voltage and Ca2+ activated K+ channels (BKCa). Since this K+ channel has a high Ca2+ sensitivity, it could be activated by the ATP-induced-Ca2+-influx, producing hyperpolarization of SMC and subsequently modulate the contractile state of these cells. Whole-cell patch clamp experiments were performed applying two consecutive voltage protocols designed by a 0.5 s voltage step from -50 to +80 mV (which evokes a BKCa current), followed by a 2 s voltage ramp from +80 to -80 mV. ATPe was added at voltage values below 0 mV, where the impulse force is favorable to produce an inward cationic current through P2X channels. Immediately after 100 µM ATPe addition we observed a significant increase in BKCa current and a significant left shift of the ramp evoked current (n=6, p