Electric field stimulation-induced guinea pig gallbladder contractions: role of calcium channels in acetylcholine release.
Gallbladder motility is modulated by intrinsic cholinergic neurons. The aims of this study were to determine: (1) the effect of electric field stimulation (EFS) on guinea pig gallbladder smooth muscle, and (2) the role of calcium channels in mediating neurotransmitter release. Gallbladder muscle strips were studied isometrically in vitro. EFS (1-16 Hz, 100 V, 0.5-msec pulse width, 30-sec train duration) was used to activate the intrinsic nerves. Exogenous acetylcholine was also used to directly stimulate the smooth muscle. EFS produced a frequency-dependent contractile response that was completely abolished by tetrodotoxin. EFS-induced contractions at 16 Hz were suppressed by 84 +/- 4% with atropine, whereas hexamethonium had no effect. The L-type calcium channel blocker, nifedipine, reduced EFS contractions by 51 +/- 4%, whereas it reduced contractions to acetylcholine by only 11 +/- 5%. The N-type calcium channel blocker, omega-conotoxin GVIA, reduced EFS-induced contractions by 22 +/- 9%, but did not affect acetylcholine-induced contractions. EFS-induced contractions of the guinea pig gallbladder are primarily mediated by activation of postganglionic cholinergic neurons. The acetylcholine release from these cholinergic neurons is regulated by L- and N-type calcium channels. The inhibitory effect of calcium channel blockers on the gallbladder seen in vivo may be in part related to inhibition of acetylcholine release from the intrinsic cholinergic nerves of the gallbladder.
Parkman
H P
HP
Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Pagano
A P
AP
Martin
J S
JS
Ryan
J P
JP
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D004558:Electric Stimulation; D005704:Gallbladder / Q000294:innervation / Q000502:physiology*; D016473:Gallbladder Emptying / Q000502:physiology*; D006168:Guinea Pigs; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D000109:Acetylcholine