T. Hayashi et al., THE ACH-INDUCED WHOLE-CELL CURRENTS IN SHEEP PAROTID SECRETORY-CELLS - DO BK CHANNELS REALLY CARRY THE ACH-EVOKED WHOLE-CELL K+ CURRENT, The Journal of membrane biology, 144(2), 1995, pp. 157-166
As in other salivary glands, the secretory cells of the sheep parotid
have a resting K+ conductance that is dominated by BK channels, which
are activated by acetylcholine (ACh) and are blocked by tetraethylammo
nium (TEA). Nevertheless, perfusion studies indicate that TEA does not
inhibit ACh-evoked fluid secretion or K+ efflux from intact sheep par
otid glands. In the present study, we have used whole-cell patch clamp
techniques to show that ACh activates K+ and Cl- conductances in shee
p parotid secretory cells by increasing intracellular free Ca2+, and w
e have compared the blocker sensitivity of the ACh-evoked whole-cell K
+ current to the previously reported blocker sensitivity of the BK cha
nnels seen in these cells. The ACh-induced whole-cell K+ current was n
ot blocked by TEA (10 mmol/l) or verapamil (100 mu mol/l), both of whi
ch block the resting K+ conductance and inhibit BK channels in these c
ells. Quinine (1 mmol/l) and quinidine (1 mmol/l), although only weak
blockers of the resting K+ conductance, inhibited the ACh-evoked curre
nt at 0 mV (K+ current), by 68% and 78%, respectively. 4-Aminopyridine
(10 mmol/l) partially inhibited the ACh-induced K+ current and caused
it to fluctuate. It also caused the resting membrane currents to fluc
tuate, possibly by altering cytosolic free Ca2+. Ba2+ (100 mu mol/l),
a blocker of the inwardly rectifying K+ conductance in sheep parotid c
ells, had no effect on the ACh-induced K+ current. We conclude that th
e ACh-induced K+ conductance in sheep parotid cells is pharmacological
ly distinct from both the outwardly rectifying (BK) K+ conductance and
the inwardly rectifying Kf conductance seen in unstimulated cells. Gi
ven that in vitro perfusion and K+ efflux studies on other salivary gl
ands in which BK channels dominate the resting conductance (e.g., the
rat mandibular, rat parotid and mouse mandibular glands) have revealed
an insensitivity to TEA, suggesting that BK channels do not carry the
ACh-evoked K+ current, we propose that BK channels do not contribute
substantially to the K+ current evoked by ACh in the secretory cells o
f most salivary glands.