TY - JOUR
T1 - An increase in persistent sodium current contributes to intrinsic neuronal bursting after status epilepticus
AU - Chen, Shmuel
AU - Su, Hailing
AU - Yue, Cuiyong
AU - Remy, Stefan
AU - Royeck, Michel
AU - Sochivko, Dmitry
AU - Opitz, Thoralf
AU - Beck, Heinz
AU - Yaari, Yoel
PY - 2011/1/1
Y1 - 2011/1/1
N2 - Brain damage causes multiple changes in synaptic function and intrinsic properties of surviving neurons, leading to the development of chronic epilepsy. In the widely used pilocarpine-status epilepticus (SE) rat model of temporal lobe epilepsy (TLE), a major alteration is the marked increase in the fraction of intrinsically bursting CA1 pyramidal cells. Here we have differentiated between two types of bursting phenotypes: 1) bursting in response to threshold-straddling excitatory current pulses (low-threshold bursting) and 2) bursting only in response to suprathreshold stimuli (high-threshold bursting). Low-threshold bursting prevailed in 46.5% of SE-experienced neurons sampled 1-4 wk after pilocarpine-SE, but was rarely seen in control neurons (1.9%). As previously shown, it appeared to be driven predominantly by a T-type Ca 2+ current (ICaT) in the apical dendrites. After blocking low-threshold bursting with Ni2+, the same neurons still manifested a high-threshold bursting phenotype. Another 40.1% of SE-experienced neurons displayed only a high-threshold bursting phenotype and the remaining 13.4% of these neurons were nonbursters. Altogether, high-threshold bursting prevailed in 86.6% of SE-experienced neurons, but only in 33.0% of control neurons. Several lines of evidence indicated that high-threshold bursting is driven by persistent Na+ current (INaP) at or near the soma. Congruently, INaP was 1.5-fold larger in SE-experienced versus control neurons. We conclude that an increase in INaP, conjointly with an increase in ICaT, strongly contributes to the predominance of bursting phenotypes in CA1 pyramidal cells early after pilocarpine-SE and thus likely plays a role in the development of a chronic epileptic condition in this TLE model.
AB - Brain damage causes multiple changes in synaptic function and intrinsic properties of surviving neurons, leading to the development of chronic epilepsy. In the widely used pilocarpine-status epilepticus (SE) rat model of temporal lobe epilepsy (TLE), a major alteration is the marked increase in the fraction of intrinsically bursting CA1 pyramidal cells. Here we have differentiated between two types of bursting phenotypes: 1) bursting in response to threshold-straddling excitatory current pulses (low-threshold bursting) and 2) bursting only in response to suprathreshold stimuli (high-threshold bursting). Low-threshold bursting prevailed in 46.5% of SE-experienced neurons sampled 1-4 wk after pilocarpine-SE, but was rarely seen in control neurons (1.9%). As previously shown, it appeared to be driven predominantly by a T-type Ca 2+ current (ICaT) in the apical dendrites. After blocking low-threshold bursting with Ni2+, the same neurons still manifested a high-threshold bursting phenotype. Another 40.1% of SE-experienced neurons displayed only a high-threshold bursting phenotype and the remaining 13.4% of these neurons were nonbursters. Altogether, high-threshold bursting prevailed in 86.6% of SE-experienced neurons, but only in 33.0% of control neurons. Several lines of evidence indicated that high-threshold bursting is driven by persistent Na+ current (INaP) at or near the soma. Congruently, INaP was 1.5-fold larger in SE-experienced versus control neurons. We conclude that an increase in INaP, conjointly with an increase in ICaT, strongly contributes to the predominance of bursting phenotypes in CA1 pyramidal cells early after pilocarpine-SE and thus likely plays a role in the development of a chronic epileptic condition in this TLE model.
UR - http://www.scopus.com/inward/record.url?scp=78651429319&partnerID=8YFLogxK
U2 - 10.1152/jn.00184.2010
DO - 10.1152/jn.00184.2010
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C2 - 20980543
AN - SCOPUS:78651429319
SN - 0022-3077
VL - 105
SP - 117
EP - 129
JO - Journal of Neurophysiology
JF - Journal of Neurophysiology
IS - 1
ER -