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Control of bursting activity by modulation of ionic currents

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Our study is focused on modulation of dynamics of single leech heart interneurons (HNs). We consider two models of HNs representing these neurons under two different pharmacological treatments: (1) blocking of Ca2+ currents and inhibitory coupling with the Ca2+-containing saline and partial blocking of K+ currents; (2) decoupling HNs with bicuculline. In (1), an HN demonstrates slow plateau-like oscillations [1, 2]. In (2), an HN demonstrates endogenously bursting activity [3]. We analyze how the interburst interval and burst duration could be controlled by manipulating hyperpolarization-activated current, I h , and persistent Na+ current, I P , namely by variation of their conductances and the half-activation voltages, V1/2. For example, burst duration increases greatly from 1.7 s to 8.9 s as Vh,1/2increased from -30 mV to 4 mV. The interburst interval grows from 0.6 s to 125 s as the Vh,1/2decreases from 4 [mV] to -56 [mV] in accordance with a saddle-node bifurcation. In (2), we similarly show that the variation of Vh,1/2could be a target for modulation of the bursting. In both cases, we show co-existence of bursting and silence. Interestingly, the co-existence is sensitive to g h (and to maximal conductance of fast Ca2+ current, gCaF too in (2)) and is not sensitive to the maximal conductances of other currents. In (1), if g h is increased from 4 nS to 8 nS, the bistability is then observed in an almost five-fold larger range of the leak conductance values, gleak. In (2), if either g h is changed from 4 nS to 8 nS or gCaF is changed from 5 nS to 0 nS, the bistability is observed in an almost two-fold larger range of gleak. If the bistability is an indication of a dysfunctional dynamics, this observation describes a new, potentially pathological role of over-expression of I h and ICaF.


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    Opdyke CA, Calabrese RL: A persistent sodium current contributes to oscillatory activity in heart interneurons of the medicinal leech. J Comp Physiol. 1994, 175: 781-789. 10.1007/BF00191850.

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    Cymbalyuk GS, Gaudry Q, Masino MA, Calabrese RL: Bursting in leech heart interneurons: cell-autonomous and network-based mechanisms. J Neurosci. 2002, 22: 10580-10592.

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This work is supported by NSF grant PHY-0750456.

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Correspondence to Gennady Cymbalyuk.

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  • Animal Model
  • Pharmacological Treatment
  • Large Range
  • Ionic Current
  • Maximal Conductance