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

ENRIQUE NICOLAS; ASUAJE AGUSTÍN; MONCADA MELISA; MARTÍN PEDRO; MILESI VERÓNICA

Río de Janeiro

Congreso; 38th World Congress of the International Union of Physiological Sciences; 2017

INTERNATIONAL UNION OF PHYSIOLOGICAL SCIENCES (IUPS)

Human vascular smooth muscle cells (SMC) exposed to extracellular ATP (ATPe) evoked a transient inward ionic current, carried by Na and Ca , 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 Ca influx could have on the SMC physiology, we focus on its possible functional coupling with the large conductance voltage and Ca activated K channels (BKCa). Since this K channel has a high Ca sensitivity, it could be activated by the ATP-induced-Ca -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 seconds (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