POTASSIUM CHANNELS IN HUMAN FETAL AIRWAY SMOOTH-MUSCLE CELLS

Ion channels underlying the resting membrane potential were examined i n human fetal airway smooth muscle (ASM). Tissue was obtained from the Medical Research Council Tissue Bank, London, UK. ASM cells were enzy matically dispersed, and ion currents were examined using a patch clam p. Although all cells were of similar size and stained intensely for v imentin, only similar to 50% stained intensely for smooth muscle alpha -actin or myosin heavy chain. Depolarization induced a tetraethylammon ium (TEA)- and charybdotoxin (ChTX)-sensitive outward current that var ied widely among cells (<50 to >2000 pA at + 100 mV), and a smaller no nselective cation current that was similar in all cells (similar to 20 pA at +100 mV). The TEA-sensitive current was associated with three t ypes of large conductance, ChTX-sensitive K+ channel: a 200-pS channel , which was active at negative potentials and low [Ca2+], as described for freshly isolated adult ASM, and two other K+ channels of 100 and 150 pS, previously observed only in adult ASM proliferating in culture . ChTX, but not 4-aminopyridine, caused a substantial depolarization i n the current clamp mode, suggesting that, in contrast to ASM from oth er species or vascular smooth muscle, large conductance K+ channels ra ther than a delayed rectifier are the major determinant of membrane po tential in this tissue. Our results show a distinct similarity between fetal ASM and adult ASM proliferating in culture. We suggest that the heterogeneity in current density and staining reflect different degre es of differentiation, rather than different cell types, and that the 100- and 150-pS K+ channels are specifically associated with a prolife rative phenotype in human ASM.