The pathophysiological roles of a voltage-gated potassium channel Kv1.5 in toluene diisocyanate-induced asthma
Y. C. Lee, K. S. Lee, H. B. Lee, Y. K. Rhee, Y. G. Kwak (Chonju, South Korea)
Source: Annual Congress 2002 - Cellular reactions in allergy in humans and animals
Session: Cellular reactions in allergy in humans and animals
Session type: Poster Discussion
Number: 303
Disease area: Airway diseases
Abstract Potassium channels in bronchial smooth muscle underlie bronchial tone by controlling the membrane potential of airway myocytes. The human Kv1.5 channel (hKv1.5) is known to be the predominant voltage-dependent current and to regulate the basal tone in human airway myocytes. In addition, toluene diisocyanate (TDI), which provokes a kind of occupational asthma, induces bronchial hyperresponsiveness in isocyanate-induced asthma. However, the pathophysiological roles of hKv1.5 channels in bronchial hyperresponsiveness has not been studied. Thus, we examined the effect of TDI on the potassium current in human bronchial smooth muscle cells and on the hKv1.5 current expressed in Ltk- cells using patch clamp techniques. In human bronchial smooth muscle cells, the predominant voltage-dependent potassium current was insensitive to tetraethylammonium (1mM) but blocked by 4-aminopyridine (300 μ M). TDI (0.1 %) slowed the activation of the current and decreased the outward potassium current in human bronchial smooth muscle cells. In addition, TDI (0.1 %) also decreased the Kv1.5 current expressed in Ltk- cells with the depolarizing shift in the voltage dependence of activation by about 50 mV. Western blot and immunohistochemical analysis showed that the protein expression level of Kv1.5 was increased in bronchial smooth muscles of TDI-sensitized and challenged mice as well as TDI-asthma patient. Interestingly, dexamethasone and MMPI-I prevented the TDI-induced alteration of Kv1.5 channel protein expression. These results clearly showed that TDI blocked Kv1.5 current and alter Kv1.5 channel protein expression, thereby maybe contributing to enhanced reactivity of bronchial muscle in TDI-induced asthma.
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Y. C. Lee, K. S. Lee, H. B. Lee, Y. K. Rhee, Y. G. Kwak (Chonju, South Korea). The pathophysiological roles of a voltage-gated potassium channel Kv1.5 in toluene diisocyanate-induced asthma. Eur Respir J 2002; 20: Suppl. 38, 303
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