ION CHANNELS IN FRESHLY ISOLATED AND CULTURED HUMAN BRONCHIAL SMOOTH-MUSCLE CELLS

Voltage-gated ion currents were studied in human bronchial airway smoo th muscle (ASM) cells. Proliferating or growth-arrested cells in cultu re were compared with freshly isolated cells. Three types of charybdot oxin (ChTX)-sensitive K+ channel were observed in all cell types, with conductances in symmetrical 140 mM KCl solutions ([Ca2+](i) < 0.1 nM) of 206 +/- 14 pS (n = 32), 144 +/- 11 pS (n = 27) and 109 +/- 5 pS (n = 25). The relative proportion of each channel type differed substant ially between the three groups of cells. In freshly isolated ASM cells large conductance K+ channels were represented almost entirely by a c onductance of 206 pS, which was found in all twenty-three patches stud ied. In contrast, in most patches from proliferating cells the majorit y of channels had conductances of either 144 pS (14 of 21 patches) or 109 pS (8 of 21 patches). Cultured cells that had been growth arrested by serum depletion revealed the same set of channels as the prolifera ting cells, but the occurrence of the 109 pS channel was much more fre quent (16 of 19 patches). As has been shown previously, 206 pS channel s were active at a physiological membrane potential (-60 to -20 mV) ev en at a very low free [Ca2+]. The 144 pS channels could be recorded on ly at depolarized potentials (+80 to +100 mV), whereas 109 pS channels were active over a wide range of potentials (-60 to +100 mV), but onl y in the presence of GTP. In a proportion of cultured cells a tetrodot oxin-sensitive Na+ current and a hyperpolarization-induced inwardly re ctifying K+ current were also observed (15 and 21%, respectively, of a ll cells examined). Neither of these currents were observed in freshly isolated cells. Whole-cell outward current in all groups was sensitiv e to tetraethylammonium, ChTX, and iberiotoxin, but not to 4-aminopyri dine. In summary, it is dear that during proliferation there are consi derable changes in the expression of ionic channels in ASM that have p rofound functional significance. In particular, these changes would te nd to make the tissue more excitable, and may be of relevance to the p roliferative process itself.