Pattern of Ca2+ increase determines the type of secretory mechanism activated in dog pancreatic duct epithelial cells.
Intracellular calcium concentration ([Ca(2+)](i)) is a key factor controlling secretion from various cell types. We investigated how different patterns of [Ca(2+)](i) signals evoke salt secretion via ion transport mechanisms and mucin secretion via exocytosis in dog pancreatic duct epithelial cells (PDEC). Activation of epithelial P2Y(2) receptors by UTP generated two patterns of [Ca(2+)](i) change: 2-10 microm UTP induced [Ca(2+)](i) oscillations, whereas 100 microm UTP induced a sustained [Ca(2+)](i) increase, both in the micromolar range. As monitored by carbon-fibre amperometry, the sustained [Ca(2+)](i) increase stimulated a larger increase in exocytosis than [Ca(2+)](i) oscillations, despite their similar amplitude. In contrast, patch-clamp recordings revealed that [Ca(2+)](i) oscillations synchronously activated a K(+) current as efficiently as the sustained [Ca(2+)](i) increase. This K(+) current was mediated by intermediate-conductance Ca(2+)-activated K(+) channels (32 pS at -100 mV) which were sensitive to charybdotoxin and resistant to TEA. Activation of these Ca(2+)-dependent K(+) channels hyperpolarized the plasma membrane from a resting potential of -40 mV to -90 mV, as monitored in perforated whole-cell configuration, in turn enhancing Na(+)-independent, Cl(-)-dependent and DIDS-sensitive HCO(3)(-) secretion, as monitored through changes in intracellular pH. PDEC therefore encode concentrations of purinergic agonists as different patterns of [Ca(2+)](i) changes, which differentially stimulate K(+) channels, the Cl(-)-HCO(3)(-) exchanger, and exocytosis. Thus, in addition to amplitude, the temporal pattern of [Ca(2+)](i) increases is an important mechanism for transducing extracellular stimuli into different physiological effects.
Jung
Seung-Ryoung
SR
Department of Physiology and Biophysics, University of Washington, Health Sciences Bldg, Seattle, 98195-7290, USA.
Kim
Kyungjin
K
Hille
Bertil
B
Nguyen
Toan D
TD
Koh
Duk-Su
DS
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002460:Cell Line; D004285:Dogs; D004594:Electrophysiology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D009077:Mucins / Q000378:metabolism; D010183:Pancreatic Ducts / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D014544:Uridine Triphosphate / Q000502:physiology
D001639:Bicarbonates; D009077:Mucins; D024681:Potassium Channels, Calcium-Activated; D000255:Adenosine Triphosphate; D002118:Calcium; D014544:Uridine Triphosphate