Changes in delayed rectifier K+ channel function and its regulation by protein kinase C pathway in bronchial myocytes from asthmatic rats.
OBJECTIVE
To investigate changes in the delayed rectifier K+ channel (Kv) function and the regulation of Kv by the protein kinase C (PKC) pathway in bronchial myocytes from asthmatic rats.


METHODS
The Kv currents and membrane potentials in bronchial myocytes from asthmatic rats and from controls were observed, using whole cell voltage- and current-patch clamp techniques.


RESULTS
Bronchial myocytes from asthmatic rats showed a significant reduction in Kv-current density (51.6 +/- 9.4 pA/pF, n = 14, P < 0.01) in comparison with those from control rats (72.4 +/- 12.3 pA/pF, n = 14) at + 50 mV. The current-voltage relationship curve exhibited a significant downward shift. Bronchial myocytes from asthmatic rats had no significantly different capacitances (P > 0.05), but had more positive membrane potential (P < 0.01) compared with those from controls. 1 micro mol/L phorbol 12-myristate 13-acetate, a PKC activator, caused an obvious reduction in Kv-current density (P < 0.01) and a significant downward shift in the current-voltage relationship curve, an effect which was partly abolished by 1 micro mol/L Ro31-8220 (a PKC inhibitor); 1 micro mol/L phorbol 12-myristate 13-acetate caused more positive membrane potential (Em), from -36.8 +/- 5.7 mV to -30.4 +/- 7.3 mV, in rat bronchial myocytes (P < 0.05). This effect was partly abolished by 1 micro mol/L Ro31-8220.


CONCLUSIONS
Bronchial myocytes from asthmatic rats have inhibited Kv function, more positive membrane potential, and higher excitability, all of which can also be induced by PKC activation. These characteristics may contribute to the development of airway hyperreactivity in asthma.
Liu
Xiansheng
X
Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Liu-xiansheng@hotmail.com
Xu
Yongjian
Y
Zhang
Zhenxiang
Z
D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000166:cytology*; D008564:Membrane Potentials; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015221:Potassium Channels; D011493:Protein Kinase C