Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC303
The gap junction opener trimethylamine enhances characteristics of network based activity within nociceptive dorsal horn
C. Kay1, D. Ursu2, E. Sher2, A. King1
1. Leeds University, Leeds, United Kingdom. 2. Eli Lilly & Co, Windlesham, United Kingdom.
Neuronal networks in the spinal dorsal horn (DH) present the first site for central integration of peripheral somatosensory inputs. The organization of such networks is not fully understood. In substantia gelatinosa (SG), 4-aminopyridine (4-AP) induces network behaviour that is disrupted by gap junction (GJ) uncouplers, demonstrating a contribution of electrical synapses(1). In this study, the effects of Trimethylamine (TMA), a gap junction opener(2), on network characteristics of 4-AP-induced activity were assessed using single electrode extracellular electrophysiology. Multi-site electrode array (MEA) technology was also utilised to characterise 4-AP induced activity dispersed across the DH. Spinal slices (transverse, 350 µm) were obtained from terminally anaesthetized (Urethane, 2g/kg i.p.) Wistar rats aged 10-14 days old. Animal procedures accorded with current UK legislation. In single electrode recordings, superfusion of 4-AP (25 µM) induced excitation within the SG which took the form of a) large amplitude population spikes and b) 4-12 Hz rhythmic activity within the inter-spike interval. Co-application of 4-AP and TMA (50 µM) increased the number of population spikes (51.0 Hz in 4-AP to 70.2 Hz in TMA & 4AP) and significantly enhanced 4-12 Hz rhythmic activity (amp= 2.59x10-6 V2, area = 9.32 x10-6 V2 in 4-AP to amp = 12.17x10-6 V2, area = 41.48x10-6 V2 in TMA & 4-AP, p<0.05). In preliminary MEA recordings, 4-AP induced patterned activity which occurred with a degree of rhythmicity in both SG and deep laminae. The spatio-temporal characteristics of this activity were modified by TMA. These data, taken together with our previous studies on the disrupting effects of gap junction uncouplers(1) on patterned behavior indicate the existence of intrinsic neuronal networks localized to nociceptive DH that rely at least partly upon electrical synapses.
Where applicable, experiments conform with Society ethical requirements