-type neurons (D) show a significantly longer recovery after a 20 pulse train than a single AP with get EPZ004777 significant SIS3 biological activity differences (P < 0.05) up to 360 ms after the initiation of the AHP. Recovery from a train fits a biexponential with time constants 46 ms and 1578 ms. The time scale in D applies also to the other panels.C2012 The Authors. The Journal of PhysiologyC2012 The Physiological SocietyJ Physiol 591.Impulse propagation after sensory neuron injuryAHP that is generated by opening KCa channels in these neurons. Furthermore, we have previously documented that AP trains lead to the accumulation of intracellular Ca2+ (Gemes et al. 2010), which resolves with a time constant of approximately 1 s, in accordance with the time for the input resistance to recover (Fig. 9D). Nonetheless, the participation of multiple mechanisms contributing to propagation failure is likely. For instance, we show that niflumic acid slows the following frequency even though it increases membrane resistance (Currie et al. 1995). This finding, however, is consistent with prior observations that Ca2+ -activated Cl- currents excite sensory neurons (Liu et al. 2010). It is also likely that the mechanisms contributing to propagation failure differ between sensory neuron subgroups. A limitation of our data is that recordings of V m in the soma may not fully reflect membrane events at the T-junction. Some assurance is offered by the recognition that axons are likewise equipped with voltage-gated Ca2+ channels and Ca2+ -activated conductances (Scholz et al. 1993; Luscher et al. 1996; Bender Trussell, 2009; Yu et al. 2010). Furthermore, recordings by others from axonal segments lacking T-junctions are consistent with our key findings, including activity-induced depression of both membrane excitability (Bostock Grafe, 1985; Waikar et al. 1996) and input resistance (David et al. 1995) during trains, and contribution of KCa channel opening to AP propagation failure (Bielefeldt Jackson, 1993).therefore contribute to shaping the frequency profile of afferent traffic in non-nociceptive A-type neurons. In C-type fibres, maximal instantaneous firing recorded in peripheral processes in response to natural noxious stimulation have been reported at rates from 20 Hz to above 80 Hz for mechanical stimuli (Koltzenburg et al. 1997; Slugg et al. 2000; Chen Levine, 2003), and from 50 Hz to above 100 Hz for thermal stimuli (Bessou Perl, 1969; Long, 1977; Kress et al. 1992). Sustained firing for 20 s at 20 Hz can be induced by cold (Leem et al. 1993). As we observed typical following frequencies at 5 Hz for C-type fibres, T-junction filtering may represent a critical mechanism regulating the afferent transmission of pain signals, possibly with distinct effects in subgroups of C-units. Conduction failure in a burst follows initial conduction success and occurs progressively with higher frequencies, so the expected perceptual effect would be akin to adaptation, such that sensations generated by activity at the high end of a neuron's dynamic range will be lessened in intensity and duration. This may serve to avoid an overwhelming or distracting percept, and to protect neuronal somata from extreme Ca2+ loads, particularly in the setting of pathological conditions such as exposure to irritants that elevate maximal firing rates (Kress et al. 1992).T-junction filtering after injuryPotential influence of T-junction filtering on sensory functionSuccessful transmission of APs through the T-junc.-type neurons (D) show a significantly longer recovery after a 20 pulse train than a single AP with significant differences (P < 0.05) up to 360 ms after the initiation of the AHP. Recovery from a train fits a biexponential with time constants 46 ms and 1578 ms. The time scale in D applies also to the other panels.C2012 The Authors. The Journal of PhysiologyC2012 The Physiological SocietyJ Physiol 591.Impulse propagation after sensory neuron injuryAHP that is generated by opening KCa channels in these neurons. Furthermore, we have previously documented that AP trains lead to the accumulation of intracellular Ca2+ (Gemes et al. 2010), which resolves with a time constant of approximately 1 s, in accordance with the time for the input resistance to recover (Fig. 9D). Nonetheless, the participation of multiple mechanisms contributing to propagation failure is likely. For instance, we show that niflumic acid slows the following frequency even though it increases membrane resistance (Currie et al. 1995). This finding, however, is consistent with prior observations that Ca2+ -activated Cl- currents excite sensory neurons (Liu et al. 2010). It is also likely that the mechanisms contributing to propagation failure differ between sensory neuron subgroups. A limitation of our data is that recordings of V m in the soma may not fully reflect membrane events at the T-junction. Some assurance is offered by the recognition that axons are likewise equipped with voltage-gated Ca2+ channels and Ca2+ -activated conductances (Scholz et al. 1993; Luscher et al. 1996; Bender Trussell, 2009; Yu et al. 2010). Furthermore, recordings by others from axonal segments lacking T-junctions are consistent with our key findings, including activity-induced depression of both membrane excitability (Bostock Grafe, 1985; Waikar et al. 1996) and input resistance (David et al. 1995) during trains, and contribution of KCa channel opening to AP propagation failure (Bielefeldt Jackson, 1993).therefore contribute to shaping the frequency profile of afferent traffic in non-nociceptive A-type neurons. In C-type fibres, maximal instantaneous firing recorded in peripheral processes in response to natural noxious stimulation have been reported at rates from 20 Hz to above 80 Hz for mechanical stimuli (Koltzenburg et al. 1997; Slugg et al. 2000; Chen Levine, 2003), and from 50 Hz to above 100 Hz for thermal stimuli (Bessou Perl, 1969; Long, 1977; Kress et al. 1992). Sustained firing for 20 s at 20 Hz can be induced by cold (Leem et al. 1993). As we observed typical following frequencies at 5 Hz for C-type fibres, T-junction filtering may represent a critical mechanism regulating the afferent transmission of pain signals, possibly with distinct effects in subgroups of C-units. Conduction failure in a burst follows initial conduction success and occurs progressively with higher frequencies, so the expected perceptual effect would be akin to adaptation, such that sensations generated by activity at the high end of a neuron's dynamic range will be lessened in intensity and duration. This may serve to avoid an overwhelming or distracting percept, and to protect neuronal somata from extreme Ca2+ loads, particularly in the setting of pathological conditions such as exposure to irritants that elevate maximal firing rates (Kress et al. 1992).T-junction filtering after injuryPotential influence of T-junction filtering on sensory functionSuccessful transmission of APs through the T-junc.
