A307 EFFECT OF SLOW SYNAPTIC EXCITATION ON MYENTERIC INTRINSIC PRIMARY AFFERENT NEURON BKCA CHANNEL ACTIVITY. (1st March 2018)

• Record Type: Journal Article
• Authors: Brown, C; Neufelk, K; Mao, Y K; Bienenstock, J; Kunze, W A
• Is Part Of: Journal of the Canadian Association of Gastroenterology. Volume 1(2018)Supplement 1
• Page Start: 533
• Page End: 533
• Publication Date: 2018-03-01
• Subjects: Gastroenterology -- Periodicals; 616.33005
• DOI: 10.1093/jcag/gwy008.308
• Languages: English
• ISSNs: 2515-2084

Abstract

Abstract: Background: The large conductance calcium dependent potassium (BKCa ) channels are expressed in a large variety of cell types including neurons where they modulate excitability and action potential shape. Within the enteric nervous system, stretch-sensitive BKCa channels are expressed on intrinsic primary afferent neurons (IPANs) where they decrease the neurons' excitability during intestinal contractions 1 . A major determinant of peristalsis is slow excitatory neurotransmission (sEPSPs) within the IPAN to IPAN sensory network, and we wondered whether such transmission might also alter BKCa channel opening. Aims: To determine if slow synaptic excitatory input alters BKCa channel activity. Methods: All experiments were performed on longitudinal-muscle myenteric preparations prepared from jejunal segment taken from freshly euthanized adult male Swiss Webster mice. Segments were placed into a 95% carbogen bubbled Krebs solution containing 2 µM nicardipine and 1 µM scopolamine, and the myenteric plexus exposed by microdissection. BKCa channel activity was recorded in situ patch clamping in cell-attached mode. BKCa channel activity was recorded at trans-patch potentials that were varied by 20 mV steps to determine voltage-sensitivity. Such recordings were performed before during and after presynaptic electrical stimulation designed to evoke postsynaptic sEPSPs. After recording the morphotype was verified by intracellular injection of a marker dye (neurobiotin). Results: Analysis of unitary channel recordings revealed increased BKCa open probability (NPo) at fixed trans-patch potentials following sEPSPs. An increased NPo which lasted 30 s to 1 min was also observed. All BKCa channels were independently voltage sensitive with increased NPo during patch depolarisation. Conclusions: This study demonstrates that sEPSPs within the enteric nervous system modulate the function of BKCa channels in IPANs adding to the mechanistic understanding of enteric synaptic transmission and providing a potential target for therapeutic modulation of enteric nervous system excitability. Funding Agencies: NSERC