Developmental Changes in Neurally Mediated Ion Transport in Piglet Distal Colon

Abstract

To better understand the role of cnteric nerves in the regulation of colonic ion transport in neonates, we examined the effects of endogenous and exogenous neurcltransmitters on ion transport across distal colonic tissues of piglets. Tissues were obtained from full-term fetuses; newborns; suckling piglets killed 1 d, 5 d, and 14 d after birth; and 21-d-old piglets that had been weaned for 2 d. Colonic tissues were stripped of external muscle layers and mounted in Ussing flux chambers. Short-circuit current (Isc), a measure of active ion transport, and transmural potential difference were lowest in fetal colons and increased during postnatal development. Tissue conductance remained constant throughout development until d 14 and then rose sharply after weaning. Blockade of enteric neural transmission with tetrodotoxin reduced basal Isc compared with control tissues in fetal, newborn, and 1-d-old piglets but had no effect in older animals. The Na+-channel blocker amiloride had no effect on basal Isc in fetal tissues but significantly reduced Isc in all other groups, with the effect increasing with age. Isc responses to electrical field stimulation of cnteric neurons were similar in fetal throughThe extrinsic and intrinsic nerves that innervate the gastrointestinal tract are important modulators of intestinal ion transport (1, 2). Neuromodulation of intestinal transport is a key w a y in which the gut processes sensory information from luminal and systemic stimuli and initiates appropriate effector mechanisms that maintain the proper consistency and composition of luminal contents (1). Although a number of studies have now identified neural pathways and specific neurotransmitters that regulate transport function, virtually all of these reports have focused o n adult animals o r humans o r at least young animals that have already been weaned. Consequently, apart from the study by Carey and Cooke (3) in 14-d-old piglets and then increased after weaning. Increases in Isc after serosal additions of carbachol (10 KM), serotonin (10 pM), or norepinephrine (10 FM) in fetal and newborn piglets were as great or greater than in the older piglets. For serotonin and norepinephrine, Isc responses rose sharply immediately after weaning. In 1-d-old piglets, Isc responses to all stimuli wcre reduced significantly by removal of C I ions from the bathing solutions. At all ages Isc responses wcre inhibited by bumctanide (10 FM) but were not affected by amiloride. These results demonstrate that colonic CI secretion evoked by endogenous or exogenous addition of neurotransmitters is well developed at an early age in piglets. The aim of the present study w a s t o examine the effects of endogenous and exogenous neurotransmitters o n colonic ion transport during postnatal development in piglets. Although the role of hormonal signals, particularly aldosterone, in mediating developmental changes in colonic ion transport has been studied in several species (4-lo), the effect of enteric neurotransmitters o n colonic

Gut function and dysfunction in young pigs: physiology

“…This transient increase in basal Isc in the proximal SI may be explained, at least partly, by fasting [13] imposed experimentally PW in our studies [6]. In the colon, the basal Isc was shown to be higher 2 d PW than in 14 d unweaned piglets [3]. This was confirmed by our recent observations [6].…”

“…This confirms earlier work comparing young sow-fed to fully weaned pigs [22,30]. The colon of weaned pigs 2 d PW was shown in vitro to have increased responses to electrical field stimulation, thus involving the enteric nervous system, but not to 5-HT, carbachol (a Ca ++ agonist) or norepinephrine [3]. Collectively these data suggest an overall decrease in intestinal sensitivity to secretagogues over age with a transient hypersensitivity to toxins the first days PW.…”

“…Curiously, at the ileum, earlier results led to conflicting results with either no change in TEER between 14 d-old and 14 wk-old piglets [51] or an increase in TEER between newborn and 21 d-old weanling piglets [72]. Colonic TEER increased 2 d PW [3]. Thus, further studies are warranted to clarify this question of changes in intestinal permeability PW.…”

Electrophysiological properties of neurones in the internal and external submucous plexuses of newborn pig small intestine.

“…Myenteric neurones with very few slow synaptic inputs have already been described in studies of the guineapig stomach (Schemann & Wood, 1989) and rectum (Tamura & Wood, 1989 (Coleman & Taylor, 1996). Indeed, the presence and extent of spontaneous synaptic activity has been used as an indicator of maturation of neural networks in the central nervous system (Kandler & Katz, 1995 (Bach & Carey, 1994). Assuming the developmental processes are similar in the' small intestine, the plasticity may involve changes within the intrinsic neuronal networks that control intestinal function.…”

“…has been used extensively in studies of the cellular mechanisms of epithelial transport (Holtug & Skadhauge, 1991). As young animals are most prone to states of malabsorption or diarrhoea, some investigations of secretory mechanisms have been performed using tissue from suckling mice (Carey & Cooke, 1989) and unweaned pigs (Bach & Carey, 1994 Bornstein, Furness & Kunze, 1994 Preliminary reports of this work have been presented to The Physiological Society (Thomsen, Pearson & Skadhauge, 1994; Thomsen, Pearson, Nielsen & Skadhauge, 1995 The main trace (A) shows after-hyperpolarizations following excitation of the neurone by three depolarizing current pulses (0 75 nA, 50 ms). The neurone had a resting membrane potential of -55 mV.…”