INCREASED SENSITIZATION OF THE MYOFILAMENTS IN RAT NEONATAL PORTAL-VEIN - A POTENTIAL MECHANISM

The contractile regulation of neonatal smooth muscle was studied in ra t neonatal portal vein. Strips of beta-escin-permeabilized portal vein from 3- to 5-day-old rats and 5- to 6-week-old rats were mounted on a 'bubble chamber' in calcium solutions buffered with 10 mM EGTA. Altho ugh the overall tension development was lower in neonatal muscle as ex pected, the calcium sensitivity of the neonatal permeabilized portal v ein was significantly higher than in developed portal vein. Endothelin -1 -induced sensitization of the myofilaments was investigated. Endoth elin-l produced an increase in tension of permeabilized neonatal porta l vein in a calcium solution buffered with 10 mM EGTA. This sensitizat ion was proportionally higher in neonatal than in developed smooth mus cle, despite similar initial submaximal calcium contractions. GTP gamm a S-induced calcium sensitization was also proportionally higher in ne onatal permeabilized strips than in fully developed smooth muscle. The se changes may be due to alterations in the intracellular signalling p athways which mediate calcium sensitization in smooth muscle. As some endothelin-1-mediated responses are known to occur via activation of t he heterotrimeric GTP-binding protein, G(q), the levels of protein exp ression of G(q) alpha were studied. In membrane preparations from neon atal rat portal vein the expression of G(q) alpha was significantly hi gher than in portal vein membrane preparations loaded with equal prote in from 5- to 6-week-old rats. In conclusion, agonist-induced sensitiz ation of the myofilaments was higher in neonatal rat portal vein than in fully developed portal vein. This difference is the result elf chan ges in intracellular signalling and may be partly produced by the grea ter expression of G(q) alpha observed in neonatal portal vein.