Functional Roles of an ERG Current Isolated in Cerebellar Purkinje Neurons

Abstract

Transcripts encoding ERG potassium channels are expressed by most neurons of the CNS. By patch-clamp whole cell recording from Purkinje neurons in slices of young (5-9 days old) mouse cerebellum we have been able to isolate a tail current [IK(ERG)] with the same characteristics as previously described for ERG channels. In zero external Ca2+ and high K+ (40 mM) the V1/2 of activation was -50.7 mV, the V1/2 of inactivation was -70.6 mV, and the deactivation rate was double exponential and voltage dependent. IK(ERG) was 93.0% blocked by WAY-123,398 (1 microM) and 78.2% by haloperidol (2 microM). The role of IK(ERG) on evoked firing was studied in adult mice, where WAY-123,398 application decreased the first spike latency, increased the firing frequency, and suppressed the frequency adaptation. However, the shape of individual action potentials was not affected. Stimulation of presynaptic climbing fibers evoked the Purkinje neuron "complex spike," composed of an initial spike and several spikelets. IK(ERG) block caused an increase of the number of spikelets of the "complex spike." These data show, for the first time, an IK(ERG) in a neuron of the CNS, the cerebellar Purkinje neuron, and indicate that such a current is involved in the control of membrane excitability, firing frequency adaptation, and in determining the effects of the climbing fiber synapse.

ERG Conductance Expression Modulates the Excitability of Ventral Horn GABAergic Interneurons That Control Rhythmic Oscillations in the Developing Mouse Spinal Cord

“…In particular, the ontogeny and functional development of GABAergic interneurons observed in vivo (Antal et al, 1994;Barbeau et al, 1999;Gao et al, 2001;Tran et al, 2003) is maintained in cultured spinal slices (Avossa et al, 2003;Furlan et al, 2005), validating the crucial importance of GABAergic connections for circuit assembly and activity (Barbeau et al, 1999). In the cultured spinal cord, ventral interneurons strongly, yet transiently, express a typical I K(ERG) (Furlan et al, 2005) that controls membrane excitability (Chiesa et al, 1997;Sacco et al, 2003) in coincidence with the appearance of developmentally regulated GABAergic markers (Avossa et al, 2003;Furlan et al, 2005).…”

“…In the present study, 7 DIV ventral interneurons (7 of 11 cells) produced an inward current when repolarized to Ϫ140 mV for 250 ms after a conditioning step to 0 mV for 15 s. Such a current was fully blocked by E4031 (Alomone Laboratories) [used at a saturating concentration of 1 M to ensure full, rapid block of I K(ERG) (Schwarz and Bauer, 1999;Bauer and Schwarz, 2001;Wimmers et al, 2001;Hirdes et al, 2005)] and was absent when preceded by a 15 s step to Ϫ70 mV. These properties are typical of I K(ERG) (Sacco et al, 2003;Furlan et al, 2005;Hirdes et al, 2005), which is usually expressed by ϳ70% of interneurons at this developmental stage (Furlan et al, 2005).…”

“…Using organotypic slice cultures as an in vitro model system of spinal network development, we have recently reported that all embryonic GABAergic interneurons express m-erg genes and ERG proteins (Furlan et al, 2005). The erg genes code for a potassium current termed I K(ERG) (Schwarz and Bauer, 2004) that possesses unusual kinetic characteristics, including fast inactivation with strong resurgent properties after hyperpolarization (Chiesa et al, 1997;Sacco et al, 2003). Because I K(ERG) is amply expressed in developing neurons and progressively disappears during neuronal maturation (Arcangeli et al, , 1998, it is a candidate mechanism for regulating the excitability of GABAergic interneurons before birth and thus for controlling the output of spinal networks.…”

Homeostatic Control of Sensory Output in Basal Vomeronasal Neurons: Activity-Dependent Expression ofEther-à-Go-Go-Related Gene Potassium Channels

“…However, gating properties vary substantially between endogenous and heterologously expressed ERG channels and between subunits (Pond and Nerbonne, 2001;Hirdes et al, 2005). So far, neuronal ERG currents have been described in cerebellar Purkinje neurons (Sacco et al, 2003) and ventral horn interneurons (Furlan et al, 2007).…”

Cholesterol regulates HERG K+channel activation by increasing phospholipase C β1 expression

“…The functional significance of HERG channel is suggested, not only in cardiac cells but also in various neuronal cells, such as hippocampal glial cells 7 and Purkinje cells. 8 Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P 2 ] plays a fundamental role in the plasma membrane, where it regulates signal transduction, exocytosis/endocytosis, actin dynamics and ion channel and transporter functions. 9,10 HERG channel is one of the ion channels under the regulation of PtdIns(4,5)P 2 .…”