Sustained norepinephrine contraction in the rat portal vein is lost when Ca(2+) is replaced with Sr(2+)

Agonist-induced activation of smoothmuscle involves a rise in intracellular Ca²⁺ concentrationand sensitization of myosin light chain phosphorylation toCa²⁺. Sr²⁺ can enter through Ca²⁺channels, be sequestered and released from sarcoplasmic reticulum, andreplace Ca²⁺ in activation of myosin light chainphosphorylation. Sr²⁺ cannot replace Ca²⁺ infacilitation of agonist-activated Ca²⁺-dependentnonselective cation channels. It is not known whether Sr²⁺can replace Ca²⁺ in small G protein-mediated sensitizationof phosphorylation. To explore mechanisms involved in-receptor-activated contractions in smooth muscle, effects ofreplacing Ca²⁺ with Sr²⁺ were examined in ratportal vein. Norepinephrine (NE) at >3.0 × 10⁷ Min the presence of Ca²⁺ resulted in a strong sustainedcontraction, whereas this sustained component was absent in thepresence of Sr²⁺; only the amplitude of phasic contractionsincreased. Pretreatment with low (~0.05 mM) free Ca²⁺followed by 2.5 mM Sr²⁺ resulted in a sustained componentof the NE response. In -escin-permeabilized preparations,phenylephrine in the presence of GTP or guanosine 5'-O-(3-thiotriphosphate) alone induced sensitization toSr²⁺. In conclusion, a Ca²⁺-regulatedmembrane/channel process is required for the sustained component of NEresponses in rat portal vein. Sensitization alone is not responsiblefor the sustained phase of the NE contraction.