Following chronic liver injury, hepatic stellate cells (HSCs) transdifferentiate 
into myofibroblast-like cells, which develop contractile properties and 
contribute to increased resistance to blood flow. We investigated whether this 
phenotypic activation includes changes in the expression of L-type 
voltage-operated Ca2+ channels (VOCC), which mediate Ca2+ influx and regulate 
cell contraction in vascular cell types. Rat HSCs were studied in the quiescent 
phenotype and after their activation in vitro (cultured on plastic for 14 days) 
and in vivo (isolated from rats with CCl(4)-induced cirrhosis). Patch-clamp 
studies showed Ca2+ currents through L-type VOCC in HSCs activated both in vitro 
and in vivo, whereas no currents were detected in quiescent HSCs. Moreover, 
binding studies with (3)H-isradipine, a specific L-type VOCC antagonist, showed 
a large number of binding sites in activated HSCs, while no specific binding was 
found in quiescent HSCs. Finally, messenger RNA (mRNA) encoding L-type VOCC was 
not detected in quiescent HSCs as assessed by reverse transcription-polymerase 
chain reaction (RT-PCR) and Northern blot analysis, whereas it was present in 
activated HSCs. Stimulation of L-type VOCC with KCl resulted in a marked 
increase in [Ca2+](i) followed by cell contraction in HSCs activated both in 
vitro and in vivo, whereas no effects were observed in quiescent HSCs. We 
conclude that the activation of HSCs is associated with up-regulation of L-type 
VOCC that mediate Ca2+ influx and cell contraction. These results may be 
relevant to the pathogenesis of portal hypertension.