Stimulated Ca2+ entry activates Cl- currents after releasing Ca2+ from the intracellular store in submandibular gland cells of the rat.
In order to examine whether Ca2+ entry is directly involved in controlling exocrine secretion, the Ca(2+)-activated Cl- currents were recorded in single and clusters of rat submandibular gland cells using the whole-cell patch-clamp method. Extracellularly applied acetylcholine (ACh, 10 nM) as well as intracellularly applied GTP gamma S and InsP3 caused repetitive transients of the Cl- currents activated by intracellular Ca2+. These responses occurred also in the absence of external Ca2+, but disappeared after several minutes. Readmission of Ca2+ to the extracellular solution restored the repetitive current transients, while introduction of Sr2+ failed to restore the current signals in spite of the presence of Sr2+ entry detected by microfluorimetry. On the other hand, direct application of Sr2+ to the cell inside caused activation of the Cl- currents although less effectively than Ca2+. When Ca2+ was introduced to the extracellular solution during an interruption of ACh stimulation after the ACh-induced depletion of intracellular Ca2+ store, the Cl- current was not elicited. However, a subsequent challenge with ACh at the same concentration in the absence of extracellular Ca2+ caused repetitive transient Cl- currents. The results suggest that in this cell type the stimulated Ca2+ entry does not by itself activate the Cl- currents but activates them indirectly by triggering Ca2+ release from the intracellular Ca2+ store which may take up Ca2+ soon after the Ca2+ entry.
Fukushi
Y
Y
Department of Physiology, Hirosaki University School of Medicine, Japan.
Suga
S
S
Kamimura
N
N
Wada
J
J
Mio
Y
Y
Nishiyama
A
A
Wakui
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000008:administration & dosage / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D013324:Strontium / Q000008:administration & dosage / Q000493:pharmacokinetics; D013363:Submandibular Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D002712:Chlorides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D015544:Inositol 1,4,5-Trisphosphate; D000109:Acetylcholine; D002118:Calcium; D013324:Strontium