Activation of Human Protease Activated Receptor 2 Dilates Veins and Resistance Vessels In Vivo

Abstract

Medical Research Society 9Pdetermined from the Ni'+-sensitive current in response to a ramp protocol, with major interfering currents blocked and [Ca2+Ii buffered to =250 nM. Current density data were well fit by the model of NCX function of Weber el al (J Gen Physiol 2001; 117:119-131), which was used to determine VMax. Compared to sham-operated controls, in LVD cells the decay of the calcium transient was slowed (RC = 2.35M.17 vs 2.87M.21 s-', p=O.03), there was reduced NCX current density ( V h = 7.69a.57 vs 12.19M.56 A/F, p<O.0001) and reduced NCX activity (2.19M.18 vs 3.0W.21 s-I, e . 0 0 3 ) . There was a significant increase in SR Ca2+ content (80.58i5.94 vs 66.26*4.07 pnolesll cell volume, p3.03) and a trend towards reduced SERCA function (3.07M.17 vs 3.51M.38 s-', ~3 . 1 5 ) . The reduction in NCX activity could impair diastolic relaxation, whilst leading to incresed SR Ca2* load, thereby increasing the frequency of arrhythmogenic spontaneous Ca2+ release.