Human temporal lobe epilepsy (TLE) is associated with bioenergetic abnormaliti es including decreased phosphocreatine (PCr) normalized to ATP. The physiologica l consequences of these metabolic alterations have not be...Human temporal lobe epilepsy (TLE) is associated with bioenergetic abnormaliti es including decreased phosphocreatine (PCr) normalized to ATP. The physiologica l consequences of these metabolic alterations have not been established.We hypot hesized that impaired bioenergetics would correlate with alterations in physiolo gical functions under conditions that strongly activate neural metabolism. We co rrelated several physiological variables obtained from epileptic human dentate g ranule cells studied in slices with hippocampal PCr/ATP measured using in vivo m agnetic resonance spectroscopy.The physiological variables included: the ability to fire multiple action potentials in response to single stimuli,the inhibitory postsynaptic potential (IPSP) conductance and the responses to a 10 Hz, 10 s st imulus train. We noted a significant negative correlation between the ability to fire multiple spikes in response to single synaptic stimulation and PCr/ATP (P < 0.03) and a positive correlation between the IPSP conductance and PCr/ATP (P < 0.05). Finally, there was a strong correlation between PCr/ATP and the recovery of the membrane potential following a stimulus train (P < 0.01), with low PCr/A TP being associated with prolonged recovery times. These data suggest that the b ioenergetic impairment seen in this tissue is associated with specific changes i n excitatory and inhibitory neuronal responses to synchronized synaptic inputs.展开更多
Pain and hyperalgesia occured when L 5 and L 6 spinal nerves were ligated. To ev aluate the electrophysiological changes that contribute to this sensory patholog y, whole cell current clamp recording was performed in ...Pain and hyperalgesia occured when L 5 and L 6 spinal nerves were ligated. To ev aluate the electrophysiological changes that contribute to this sensory patholog y, whole cell current clamp recording was performed in DRGs that was obtained from neuropathic pain and control rats. After nerve ligation, action potential threshold reduced (more negative) in b oth small and median sized DRG neurons (-18.98±0.69 mV vs -11.12±1.06 mV in c ontrol small sized neurons; -19.44 ±2.22 mV vs -14.55±1.81 mV in control m edi an sized neurons), but resting membrane potential action potential duration at half amplitude (APD 1/2 ) and action potential amplitude did not change sign ifica ntly. In addition, obvious membrane potential oscillations were observed in smal l sized DRG neurons from neuropathic pain rats (P<0.05 compared with control group). These results suggested that neuropathic pain increased the exci tability of nociceptors, which may be an important mechanism underlying peripher al hypersensitivity.展开更多
文摘Human temporal lobe epilepsy (TLE) is associated with bioenergetic abnormaliti es including decreased phosphocreatine (PCr) normalized to ATP. The physiologica l consequences of these metabolic alterations have not been established.We hypot hesized that impaired bioenergetics would correlate with alterations in physiolo gical functions under conditions that strongly activate neural metabolism. We co rrelated several physiological variables obtained from epileptic human dentate g ranule cells studied in slices with hippocampal PCr/ATP measured using in vivo m agnetic resonance spectroscopy.The physiological variables included: the ability to fire multiple action potentials in response to single stimuli,the inhibitory postsynaptic potential (IPSP) conductance and the responses to a 10 Hz, 10 s st imulus train. We noted a significant negative correlation between the ability to fire multiple spikes in response to single synaptic stimulation and PCr/ATP (P < 0.03) and a positive correlation between the IPSP conductance and PCr/ATP (P < 0.05). Finally, there was a strong correlation between PCr/ATP and the recovery of the membrane potential following a stimulus train (P < 0.01), with low PCr/A TP being associated with prolonged recovery times. These data suggest that the b ioenergetic impairment seen in this tissue is associated with specific changes i n excitatory and inhibitory neuronal responses to synchronized synaptic inputs.
文摘Pain and hyperalgesia occured when L 5 and L 6 spinal nerves were ligated. To ev aluate the electrophysiological changes that contribute to this sensory patholog y, whole cell current clamp recording was performed in DRGs that was obtained from neuropathic pain and control rats. After nerve ligation, action potential threshold reduced (more negative) in b oth small and median sized DRG neurons (-18.98±0.69 mV vs -11.12±1.06 mV in c ontrol small sized neurons; -19.44 ±2.22 mV vs -14.55±1.81 mV in control m edi an sized neurons), but resting membrane potential action potential duration at half amplitude (APD 1/2 ) and action potential amplitude did not change sign ifica ntly. In addition, obvious membrane potential oscillations were observed in smal l sized DRG neurons from neuropathic pain rats (P<0.05 compared with control group). These results suggested that neuropathic pain increased the exci tability of nociceptors, which may be an important mechanism underlying peripher al hypersensitivity.