Epithelial responses evoked by stimulation of submucosal neurons in guinea pig distal colon

Abstract

The influence of submucosal neurons on ion transport in the guinea pig distal colon was examined in muscle-stripped sheets of submucosa-mucosa set up in Ussing flux chambers. Spontaneous variations in potential differences (PD) and short-circuit current occurred ranging from positive currents associated with luminal negative PDs to negative currents with luminal positive PDs. Basal current in both groups was reduced by mucosal amiloride. In tissues with positive or negative short-circuit currents, unidirectional mucosal-to-serosal sodium fluxes were greater than serosal-to-mucosal fluxes and small net absorptive fluxes were present. Little or no chloride secretory flux was present. Electrical stimulation of submucosal neurons evoked a tetrodotoxin-sensitive increase in short-circuit current in tissues with positive or negative short-circuit currents. This was due to an increase in net chloride flux and little change in net sodium flux or residual flux. The increase in net chloride flux was due almost entirely to an increase in serosal-to-mucosal chloride flux and was associated with an increase in total tissue conductance. The stimulus-evoked response was reduced by atropine. These results suggest that stimulation of submucosal neurons that innervate the distal colonic epithelium evokes a large chloride secretory response that is due in part to release of acetylcholine at neuro-enterocyte junctions.

Cholinergic inhibition of electrogenic sodium absorption in the guinea pig distal colon

“…Intramural neurons were electrically stimulated by passing a current parallel to the plane of the tissue via a pair of aluminum foil electrodes placed on the serosal surface of the tissue as reported by Cooke (5,22). Bipolar rectangular 5-mA current pulses of 1-ms duration (0.5-ms duration in each direction) were delivered at 10 Hz.…”

“…The unidirectional transmural flux of 22 Na ϩ was measured under short-circuit conditions. The mucosal-to-serosal (Jms) and serosal-to-mucosal (Jsm) flux values were measured in adjacent tissues that had Gt values differing by Ͻ30%.…”

“…This study investigates the role of submucosal cholinergic neurons in regulating electrogenic Na ϩ absorption in distal colon. Amiloride-sensitive short-circuit current (Isc) and 22 Na ϩ flux were measured in mucosal and mucosalsubmucosal preparations mounted in Ussing chambers. In the mucosal preparation, carbachol (CCh) added to the serosal side inhibited amiloride-sensitive Isc and amiloride-sensitive 22 Na ϩ absorption.…”

“…Amiloride-sensitive short-circuit current (Isc) and 22 Na ϩ flux were measured in mucosal and mucosalsubmucosal preparations mounted in Ussing chambers. In the mucosal preparation, carbachol (CCh) added to the serosal side inhibited amiloride-sensitive Isc and amiloride-sensitive 22 Na ϩ absorption. The inhibitory effect of CCh was observed at ϳ0.1 M, and maximum inhibition of ϳ70% was attained at ϳ30 M (IC50 ϭ ϳ1 M).…”

“…The purpose of this study is, therefore, to elucidate the regulation of electrogenic Na ϩ absorption by enteric submucosal neurons, particularly the cholinergic type, in an isolated guinea pig distal colon mounted in an Ussing chamber. We examined the effect of CCh on the amiloride-sensitive short-circuit current (I sc ) and 22 Na ϩ flux. We also investigated the effect of stimulating submucosal cholinergic neurons on electrogenic Na ϩ absorption by using electrical field stimulation (EFS).…”