Ion currents in smooth muscle cells from human small bronchioles: Presenceof an inward rectifier K+ current and three types of large conductance K+ channel

Bronchoconstriction of small bronchioles plays a major role in the increase in airway resistance following agonist challenge. There is evidence that t he airway smooth muscle (ASM) of small bronchioles differs functionally fro m that in larger airways. Little is known however about the electrophysiolo gy of small bronchioles. Ion currents were therefore studied in airway smoo th muscle cells freshly dissociated from human intralobular bronchioles, wi th a diameter between 0.3 and 1.0 mm. As previously reported for human larg e airways, the major outward current in these cells was due to activity of large conductance K+ (BK) channels, with a relatively minor component due t o a voltage-gated delayed rectifier current (I-DR), which was only observed in similar to 30 % of cells. Three distinct types of iberiotoxin- and TEA- sensitive large conductance K+ channel contributed to large conductance Kcurrent (I-BK). These included a highly voltage- and Ca2+-sensitive 200 pS channel previously reported in human large airways, and two smaller channel s of 150 and 100 pS previously seen only in human fetal or cultured ASM. In contrast to large airways, ASM cells from bronchioles also demonstrated a voltage-gated inward rectifier current (I-IR). I-IR was activated by hyperp olarisation below the K+ equilibrium potential and could be blocked by subm illimolar concentrations of Cs+ or Ba2+, and partially by physiological con centrations of Na+. Corresponding single channels with a conductance of sim ilar to 17 pS could also be recorded in the cell-attached configuration. A small voltage-independent current was also observed which was resistant to classic K+ and Cl- channel blockers but which could be abolished by replace ment of Naf with the impermeant cation N-methyl-D-glucamine (NMDG(+)). Corr esponding non-selective single channels of similar to 20 pS could be seen i n inside-out mode. These results demonstrate that ASM from small bronchiole s differs in terms of ion currents and channels from ASM derived from large airways, with possible implications for function.