Parathyroid hypertensive factor inhibits voltage-gated K+ channels in vascular smooth muscle cells

Parathyroid hypertensive factor (PHF) has been implicated in regulation of vascular smooth muscle tone and pathogenesis of several forms of hypertensi on. Earlier studies have suggested that PHF enhances the actions of other v asoconstrictors, while it has no in vitro vasoconstrictor property of its o wn. PHF was previously found to enhance the L-type Ca channel currents and intracellular Ca responses to depolarization in vascular smooth muscle cell s (VSMCs). The present study examined whether PHF might act on K channels i n the plasma membrane of VSMCs. Primary cultured VSMCs from rat tail artery were used. The whole-cell version of the patch-clamp technique was used un der conditions in which there was no contribution of Ca-activated K channel s to the outward current. Both purified and semipurified PHF inhibited the delayed rectifier type potassium current in a dose-dependent manner. The ef fect was time dependent and was first significantly different from the cont rol current after 30 min. The inhibition of the delayed rectifier K channel was associated with a time-dependent decrease in the resting membrane pote ntial. Therefore, PHF may alter VSMC cellular Ca responses by reducing the membrane potential to a level closer to the activation potential of Ca chan nels.