Control of bursting activity by modulation of ionic currents

Abstract

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, Ih, and persistent Na+ current, IP, 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,1/2 increased from -30 mV to 4 mV. The interburst interval grows from 0.6 s to 125 s as the Vh,1/2 decreases from 4 [mV] to -56 [mV] in accordance with a saddlenode bifurcation. In (2), we similarly show that the variation of Vh,1/2 could 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 gh (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 gh 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 gh 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 overexpression of Ih and ICaF.