Abstract
Recent functional evidence suggests that intermediate conductance calcium-activated potassium channels (IK channels) occur in neurons in the small intestine and in mucosal epithelial cells in the colon. This study was undertaken to investigate whether IK channel immunoreactivity occurs at these and at other sites in the gastrointestinal tract of the rat. IK channel immunoreactivity was found in nerve cell bodies throughout the gastrointestinal tract, from the esophagus to the rectum. It was revealed in the initial segments of the axons, but not in axon terminals. The majority of immunoreactive neurons had Dogiel type II morphology and in the myenteric plexus of the ileum all immunoreactive neurons were of this shape. Intrinsic primary afferent neurons in the rat small intestine are Dogiel type II neurons that are immunoreactive for calretinin, and it was found that almost all the IK channel immunoreactive neurons were also calretinin immunoreactive. IK channel immunoreactivity also occurred in calretinin-immunoreactive, Dogiel type II neurons in the caecum. Epithelial cells of the mucosal lining were immunoreactive in the esophagus, stomach, small and large intestines. In the intestines, the immunoreactivity occurred in transporting enterocytes, but not in mucous cells. Immunoreactivity was at both the apical and basolateral surfaces. A small proportion of mucosal endocrine cells was immunoreactive in the duodenum, ileum and caecum, but not in the stomach, proximal colon, distal colon or rectum. There was immunoreactivity of vascular endothelial cells. It is concluded that IK channels are located on cell bodies and proximal parts of axons of intrinsic primary afferent neurons, where, from functional studies, they would be predicted to lower neuronal excitability when opened in response to calcium entry. In the mucosa of the small and large intestine, IK channels are probably involved in control of potassium exchange, and in the esophageal and gastric mucosa they are possibly involved in control of cell volume in response to osmotic challenge.
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References
Arnold SJ, Facer P, Yiangou Y, Chen MX, Plumpton C, Tate SN, Bountra C, Chan CLH, Williams NS, Anand P (2002) Decreased potassium channel IKI and its regulator neurotrophin-3 (NT-3) in inflamed human bowel. Neuroreport 14:191–195
Boettger MK, Till S, Chen MX, Anand U, Otto WR, Plumpton C, Trezise DJ, Tate SN, Bountra C, Coward K, Birch R, Anand P (2002) Calcium-activated potassium channel SK1- and IK1-like immunoreactivity in injured human sensory neurones and its regulation by neurotrophic factors. Brain 125:252–263
Clerc N, Furness JB, Bornstein JC, Kunze WAA (1998) Correlation of electrophysiological and morphological characteristics of myenteric neurons of the duodenum in the guinea-pig. Neuroscience 82:899–914
Furness JB, Costa M (1987) The enteric nervous system. Churchill Livingstone, Edinburgh
Furness JB, Kunze WAA, Bertrand PP, Clerc N, Bornstein JC (1998) Intrinsic primary afferent neurons of the intestine. Prog Neurobiol 54:1–18
Furness JB, Trussell DC, Pompolo S, Bornstein JC, Smith TK (1990) Calbindin neurons of the guinea-pig small intestine: quantitative analysis of their numbers and projections. Cell Tissue Res 260:261–272
Gerlach AC, Gangopadhyay NN, Devor DC (2000) Kinase-dependent regulation of the intermediate conductance, calcium-dependent potassium channel, hIK1. J Biol Chem 275:585–598
Hirst GDS, Spence I (1973) Calcium action potentials in mammalian peripheral neurones. Nature 243:54–56
Hirst GDS, Holman ME, Spence I (1974) Two types of neurones in the myenteric plexus of duodenum in the guinea-pig. J Physiol (Lond) 236:303–326
Hirst GDS, Johnson SM, van Helden DF (1985) The slow calcium-dependent potassium current in a myenteric neurone of the guinea-pig ileum. J Physiol (Lond) 361:315–337
Joiner WJ, Basavappa S, Vidyasagar S, Nehrke K, Krishnan S, Binder HJ, Boulpaep EL, Rajendran VM (2003) Active K+ secretion occurs through multiple types of KCa channels and is regulated by IKCa channels in rat proximal colon. Am J Physiol 285:G185–G196
Kunze WAA, Bornstein JC, Furness JB, Hendriks R, Stephenson DSH (1994) Charybdotoxin and iberiotoxin but not apamin abolish the slow after-hyperpolarization in myenteic plexus neurons. Pflugers Arch Eur J Physiol 428:300–306
Kunze WAA, Clerc N, Furness JB, Gola M (2000) The soma and neurites of primary afferent neurons in the guinea-pig intestine respond differentially to deformation. J Physiol (Lond) 526:375–385
Lomax AEG, Sharkey KA, Bertrand PP, Low AM, Bornstein JC, Furness JB (1999) Correlation of morphology, electrophysiology and chemistry of neurons in the myenteric plexus of the guinea-pig distal colon. J Auton Nerv Syst 76:45–61
Mann PT, Southwell BR, Ding YQ, Shigemoto R, Mizuno N, Furness JB (1997) Localisation of neurokinin 3 (NK3) receptor immunoreactivity in the rat gastrointestinal tract. Cell Tissue Res 289:1–9
Mann PT, Furness JB, Southwell BR (1999) Choline acetyltransferase immunoreactivity of putative intrinsic primary afferent neurons in the rat ileum. Cell Tissue Res 297:241–248
Neylon CB, Lang RJ, Fu Y, Bobik A, Reinhart PH (1999) Molecular cloning and characterization of the intermediate-conductance Ca2+-activated K+ channel in vascular smooth muscle. Relationship between KCa channel diversity and smooth muscle cell function. Circ Res 85:e33–e43
North RA (1973) The calcium-dependent slow after-hyperpolarization in myenteric plexus neurone with tetrodotoxin-resistant action potentials. Br J Pharmacol 49:709–711
North RA, Nishi S (1974) Properties of the ganglion cells of the myenteric plexus of the guinea-pig ileum determined by intracellular recording. In: Daniel EE (ed) Proceedings 4th international symposium on gastrointestinal motility. Mitchell Press, Vancouver, pp 667–676
North RA, Nishi S (1976) The slow after-hyperpolarization of myenteric neurons. In: Bülbring E, Kostyuk PG, Shuba MF (eds) Physiology of smooth muscle. Raven Press, New York, pp 303–307
Nurgali K, Furness JB, Stebbing MJ (2003) Correlation of electrophysiology, shape and synaptic properties of myenteric AH neurons of the guinea-pig distal colon. Autonom Neurosci 103:50–64
Pompolo S, Furness JB (1988) Ultrastructure and synaptic relationships of calbindin-reactive, Dogiel type II neurons, in myenteric ganglia of guinea-pig small intestine. J Neurocytol 17:771–782
Rugiero F, Gola M, Kunze WAA, Reynaud J-C, Furness JB, Clerc N (2002) Analysis of whole cell currents by patch clamp of guinea-pig myenteric neurones in intact ganglia. J Physiol (Lond) 538:447–463
Sah P (1996) Ca2+-activated K+ currents in neurones: types, physiological roles and modulation. Trends Neurosci 19:150–154
Sah P, Bekkers JM (1996) Apical dendritic location of slow afterhyperpolarization current in hippocampal pyramidal neurons: implications for the integration of long-term potentiation. J Neurosci 16:4537–4542
Sah P, Faber ESL (2002) Channels underlying neuronal calcium-activated potassium currents. Prog Neurobiol 66:345–353
Song ZM, Brookes SJH, Costa M (1991) Identification of myenteric neurons which project to the mucosa of the guinea-pig small intestine. Neurosci Lett 129:294–298
Tamura K, Ito H, Wade PR (2001) Morphology, electrophysiology, and calbindin immunoreactivity of myenteric neurons in the guinea pig distal colon. J Comp Neurol 437:423–437
Vandorpe DH, Shmukler BE, Jiang L, Lim, B, Maylie J, Adelman JP, de Franceschi L, Cappellini MD, Brugnara C., Alper SL (1998) cDNA cloning and functional characterization of the mouse Ca2+-gated K+ channel, mIK1. Roles in regulatory volume decrease and erythroid differentiation. J Biol Chem 273:21542–21553
Vergara C, Latorre R, Marrion NV, Adelman JP (1998) Calcium-activated potassium channels. Curr Opin Cell Biol 8:321–329
Vogalis F, Furness JB, Kunze WAA (2001) Afterhyperpolarization current in myenteric neurons of the guinea pig duodenum. J Neurophysiol 85:1941–1951
Vogalis F, Harvey JR, Furness JB (2002a) TEA- and apamin-resistant KCa channels in guinea-pig myenteric neurons: slow AHP channels. J Physiol (Lond) 538:421–433
Vogalis F, Harvey JR, Neylon CB, Furness JB (2002b) Regulation of K+ channels underlying the slow afterhyperpolarization in enteric afterhyperpolarization-generating myenteric neurons: role of calcium and phosphorylation. Clin Exp Pharmacol Physiol 29:935–943
Wang J, Morishima S, Okada Y (2003) IK channels are involved in the regulatory volume decrease in human epithelial cells. Am J Physiol 284:C77–C84
Wood JD (1987) Physiology of the enteric nervous system. In: Johnson LR (ed) Physiology of the gastrointestinal tract. Raven Press, New York, pp 67–100
Acknowledgements
These studies were funded by the National Health and Medical Research Council (Australia) and GlaxoSmithKline. Dr. Annette Kirchgessner is thanked for her guidance and discussion. We thank Katrina Ngui and Daniel Poole for assistance with the immunohistochemical studies and imaging.
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Furness, J.B., Robbins, H.L., Selmer, IS. et al. Expression of intermediate conductance potassium channel immunoreactivity in neurons and epithelial cells of the rat gastrointestinal tract. Cell Tissue Res 314, 179–189 (2003). https://doi.org/10.1007/s00441-003-0808-z
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DOI: https://doi.org/10.1007/s00441-003-0808-z