Basolateral K+ efflux is largely independent of maxi-K+ channels in rat submandibular glands during secretion.
The involvement of large-conductance, voltage- and Ca(2+)-activated K+ channels (maxi-K+ channels) in basolateral Ca(2+)-dependent K(+)-efflux pathways and fluid secretion by the rat submandibular gland was investigated. Basolateral K+ efflux was monitored by measuring the change in K+ concentration in the perfusate collected from the vein of the isolated, perfused rat submandibular gland every 30 s. Under conditions in which the Na+/K(+)-ATPase and Na(+)-K(+)-2Cl- cotransporter were inhibited by ouabain (1 mmol/l) and bumetanide (50 mumol/l) respectively, continuous stimulation with acetylcholine (ACh) (1 mumol/l) caused a transient large net K+ efflux, followed by a smaller K+ efflux, which gradually returned to the basal level within 10 min. These two components of the K+ efflux appear to be dependent on an increase in cytosolic Ca2+ concentration. The initial transient K+ efflux was not affected by charybdotoxin (100 nmol/l) or tetraethylammonium (TEA) (5 mmol/l) but the smaller second component was strongly and reversibly inhibited by charybdotoxin (100 nmol/l) and TEA (0.1 and 5 mmol/l). The initial K+ efflux transient induced by ACh was inhibited by quinine (0.1-3 mmol/l), quinidine (1-3 mmol/l) and Ba2+ (5 mmol/l), but not by verapamil (0.1 mmol/l), lidocaine (1 mmol/l), 4-aminopyridine (1 mmol/l) or apamin (1 mumol/l). Ca(2+)-dependent transient large K+ effluxes induced by substance P (0.01 mumol/l) and A23187 (3 mumol/l) were not inhibited by TEA (5 mmol/l or 10 mmol/l). A23187 (3 mumol/l) evoked a biphasic fluid-secretory response, which was not inhibited by TEA (5 mmol/l). Patch-clamp studies confirmed that the whole-cell outward K+ current attributable to maxi-K+ channels obtained from rat submandibular endpiece cells was strongly inhibited by the addition of TEA (1-10 mmol/l) to the bath. It is concluded that maxi-K+ channels are not responsible for the major part of the Ca(2+)-dependent basolateral K+ efflux and fluid secretion by the rat submandibular gland.
Ishikawa
T
T
Department of Molecular Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
Murakami
M
M
Seo
Y
Y
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D000001:Calcimycin / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D004553:Electric Conductivity; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D028021:Sodium-Potassium-Chloride Symporters; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013363:Submandibular Gland / Q000378:metabolism* / Q000502:physiology; D013373:Substance P / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D002352:Carrier Proteins; D015221:Potassium Channels; D028021:Sodium-Potassium-Chloride Symporters; D013757:Tetraethylammonium Compounds; D013373:Substance P; D000001:Calcimycin; D010042:Ouabain; D019789:Tetraethylammonium; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine; D011188:Potassium