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The effect of protein kinase C (PKC) on force and intracellular Ca in uterine smooth muscle from pregnant women
Author(s) -
Fomin Victor P,
Kronbergs Andris,
Zhang Wenwu,
Gunst Susan
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1242-c
The importance of protein kinase C (PKC) in smooth muscle contraction is well documented. However, the role of PKC in uterine smooth muscle contraction remains unclear. Objective This study was planned to elucidate the effect of PKC on contraction and intracellular Ca concentration ([Ca 2+ ] I ) in uterine smooth muscle(myometrium) from pregnant women. We also sought to understand if the uterine cells actin cytoskeleton is involved in the PKC effect Methods The effect of PKC was studied by simultaneously measuring uterine contraction and [Ca 2+ ] I in fura‐2 loaded myometrial strips using force transducer equipped spectrofluorometer. The globular (G) and filamentous (F) actin in the muscle strips were determined by Western blotting. Results The PKC activator phorbol 12,13‐dibutyrate (PDBu) increased the muscle basal tone (tonic contraction) in time and dose dependent manner with a maximal effect at 10 −6 M PDBu without affecting resting [Ca 2+ ] I . The effect was also seen in Ca‐free media. PKC inhibitor GF109203X used at 10 −6 M significantly decreased the PDBu effect on the basal tone without affecting the [Ca 2+ ] I levels. PDBu and oxytocin increased actin F/G ratio at the rate similar to the one of the force increase. Conclusion It is suggested that PKC affects human myometrial contraction by increasing phosphorylation of myosin light chain partially in Ca‐independent manner. PKC also stimulates the contraction by shifting the actin dynamic balance from the G to the F form. (Supported by NIH R55 HD45802).