Ca2+ channel blockade inhibits gallbladder ion transport.
Recent studies suggest that cholesterol gallstone (GS) formation is characterized by altered gallbladder epithelial ion transport and increased gallbladder (GB) luminal Ca2+. Moreover, intracellular Ca2+ has been reported to be an important modulator of intestinal ion transport. The aim of the present study was to determine the effects of Ca2+ channel inhibition on GB ion transport. Prairie dog GBs were mounted in a Ussing chamber and bathed in warm oxygenated Ringer's solution, and short-circuit current (Isc), transepithelial potential difference (Vms), and tissue resistance (Rt) were recorded. Following stabilization, the mucosal surfaces of the GBs were exposed to 1 or 0.1 mM verapamil (VER). Effects on Isc were apparent within 10 sec with nadir values reached in 5 +/- 1 min. Profound (76%) inhibition of Isc was seen with 1 mM verapamil exposure (26 +/- 6 microA.cm-2) as compared to baseline values (170 +/- 6 microA.cm-2) (P less than 0.001). Verapamil exposure (1 mM) also led to a marked inhibition of Vms (P less than 0.001, vs baseline) and a significant increase in Rt (P less than 0.05 vs baseline). Similar trends were seen using 0.1 mM verapamil (Isc nadir 133 +/- 13 microA.cm-2). Verapamil-induced effects on gallbladder electrophysiology were largely reversible (75-90% recovery of baseline Isc after tissue washing). These data suggest that (1) verapamil induces rapid but reversible inhibition of ion transport and (2) Ca2+ channel blockade inhibits ion transport in a dose-dependent fashion. We would propose that intracellular Ca2+ may be a regulator of GB ion transport.
Saunders
K D
KD
Research Service, Sepulveda Veterans Administration Medical Center, California.
Cates
J A
JA
Abedin
M Z
MZ
Kleinman
R
R
Roslyn
J J
JJ
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D004553:Electric Conductivity; D004594:Electrophysiology; D004848:Epithelium / Q000502:physiology; D005704:Gallbladder / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008854:Microscopy, Electron; D012589:Sciuridae / Q000502:physiology*; D013806:Theophylline / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D013806:Theophylline; D014700:Verapamil