Repetitive transcranial magnetic stimulation (rTMS) is able to induce alteration in cortical activity and excitability that outlast the period of stimulation, which is long-term depre-ssion (LTD) or long-term potentiation (LTP)-like. Accumulating evidence shows that Na(+), Ca(2+) and K(+) channels are important for the regulation of neuronal excitability. To investigate the possible mechanisms of rTMS on regulation of intrinsic excitability in hippocampal neurons, the male or female Sprague-Dawley rats aged 2-3 d or 7-8 d were treated with 14 or 7-d's low frequency (1 Hz) rTMS (400 stimuli/d), respectively. After that, the effects of rTMS on ion channels such as Na(+)-channel, A-type K(+)-channel and Ca(2+)-channel in rat hippocampal CA1 pyramidal neurons were performed by standard whole-cell patch-clamp technique. The results showed that the peak amplitude and maximal rise slope of evoked single action potential (AP) were significantly increased after 14-d's rTMS treatment. Meanwhile, the AP threshold was significantly more depolarized in neurons after 14-d's rTMS treatment than neurons in control group that without rTMS treatment. The spontaneous excitatory post-synaptic currents (sEPSCs) frequency and amplitude of CA1 pyramidal neurons in groups with rTMS treatment (both 7 d and 14 d) were obviously increased compared with the age-matched control group. Furthermore, we found that electrophysiological properties of Na(+)-channel were markedly changed after rTMS treatment, including negative-shifted activation and inactivation curves, as well as fasten recovery rate. After rTMS application, the IA amplitude of K(+)-channel was reduced; the activation and inactivation curves of K(+)-channel were significantly shifted to right. Time constant of recovery from inactivation was also more rapid. Moreover, rTMS induced an obvious increment in the maximal current peak amplitude of Ca(2+)-channel. At the same time, there was a significant rightward shift in the activation curve and inactivation curves of Ca(2+)-channel. These data suggest that rTMS can enhance the AP and sEPSCs of hippocampal CA1 neurons. Altered electrophysiological properties of Na(+)-channel, A-type K(+) channels and Ca(2+) channels contribute to the underling mechanisms of rTMS-induced up-regulation of neural excitability.

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http://dx.doi.org/10.1016/j.brainres.2013.04.053DOI Listing

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