Parathyroid hormone selectively inhibits L-type calcium channels in single vascular smooth muscle cells of the rat

Abstract

1. The active synthetic N-terminal fragment of bovine parathyroid hormone, bPTH-(1-34) at a concentration of 1 microM, decreased the peak amplitude of the long-lasting (L-type) calcium channel current by 37% (n = 14, P less than 0.01) in rat tail artery smooth muscle cells. By contrast, this fragment of parathyroid hormone (PTH) (1 microM) had no effect on the transient (T-type) calcium channel current in the same cell preparation. 2. The inhibitory effect of bPTH-(1-34) on L-channel currents was reversible and could be antagonized by the L-channel agonist, Bay K 8644. In contrast, bPTH-(1-34) inhibited Bay K 8644-induced amplification of L-channel currents. 3. The inhibitory effect of bPTH-(1-34) on L-Channel currents was dose dependent with a threshold concentration of less than 10(-7), and voltage dependent with increased inhibition at more positive holding potentials. However, this effect of bPTH-(1-34) was not dependent on different pulse lengths or interpulse intervals. 4. The kinetics of deactivation of L-channel currents were not changed although the instantaneous amplitude of the L-channel tail current was reduced by bPTH-(1-34). 5. Application of bPTH-(1-34) antagonists (10(-6) M-bPTH-(3-34) and 10(-5) M-bPTH-(7-34] did not result in any significant change in the magnitude of L-channel currents (n = 15 and n = 7, respectively). 6. Pre-incubation of cells with bPTH-(3-34) for more than 15 min abolished the inhibitory effect of bPTH-(1-34) on L-channel currents. 7. The present study provides direct evidence to demonstrate the PTH, an endogenous circulating hormone, is a selective inhibitor of L-channel currents in vascular smooth muscle cells.