The effect of protein kinase C on voltage-gated potassium channel in pulmonary artery smooth muscle cells from rats exposed to chronic hypoxia.
BACKGROUND
Chronic hypoxia can cause pulmonary hypertension and pulmonary heart disease with high mortality. The signal transduction pathway of protein kinase C (PKC) plays an important role in chronic pulmonary hypertension. So it is necessary to investigate the effect of PKC on voltage-gated potassium (K+) channels in pulmonary artery smooth muscle cells of rats exposed to chronic hypoxia.


METHODS
Male Wistar rats were randomly divided into a control group (group A) and a chronic hypoxia group (group B). Group B received hypoxia [oxygen concentration (10 +/- 1)%] eight hours per day for four consecutive weeks. Single pulmonary artery smooth muscle cells were obtained using an acute enzyme separation method. Conventional whole cell patch clamp technique was used to record resting membrane potential, membrane capacitance and voltage-gated K+ currents. The changes in voltage-gated K+ currents before and after applying paramethoxyamphetamine (PMA) (500 nmol/L), an agonist of PKC, and PMA plus carbohydrate mixture of glucose, fructose and xylitol (GFX) (30 nmol/L), an inhibitor of PKC, were compared between the two groups.


RESULTS
The resting membrane potential in group B was significantly lower than that of group A: -(29.0 +/- 4.8) mV (n = 18) vs -(42.5 +/- 4.6) mV (n = 35) (P < 0.01). But there was no change in membrane capacitance between the two groups: (17.9 +/- 4.6) pF (n = 40) vs (19.7 +/- 5.8) pF (n = 31) (P > 0.05). The voltage-gated K+ currents were significantly inhibited by PMA in group A, and this effect was reversed by GFX. However, the voltage-gated K+ currents in group B were not affected by PMA.


CONCLUSIONS
The resting membrane potential and voltage-gated K+ currents in pulmonary artery smooth muscle cells from rats exposed to chronic hypoxia decreased significantly. It seems that PKC has different effects on the voltage-gated K+ currents of pulmonary artery smooth muscle cells under different conditions.
Zhang
Yong-chang
YC
Department of Respiratory Disease, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China. vtycz@yahoo.com.cn
Ni
Wang
W
Zhang
Zhen-kiang
ZK
Xu
Yong-jian
YJ
D000818:Animals; D002908:Chronic Disease; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D011651:Pulmonary Artery / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D024642:Potassium Channels, Voltage-Gated; D011493:Protein Kinase C