Differential expression of voltage‐activated calcium channels in III and XII motoneurones during development in the rat

Abstract

To further our understanding of the role that voltage-activated Ca2+ channels play in the development, physiology and pathophysiology of motoneurones (MNs), we used whole-cell patch-clamp recording to compare voltage-activated Ca2+ currents in oculomotor (III) and hypoglossal (XII) MNs of neonatal [postnatal day (P)1-5] and juvenile (P14-19) rats. In contrast to III MNs that innervate extraocular muscles, XII MNs that innervate tongue muscles mature more rapidly, fire bursts of low frequency action potentials and are vulnerable to degeneration in amyotrophic lateral sclerosis. In neonates, low voltage-activated (LVA) Ca2+ current densities are similar in XII and III MNs but high voltage-activated (HVA) Ca2+ current densities are twofold higher in XII MNs. The HVA Ca2+ channel antagonists (nimodipine and nifedipine for L-type, omega-agatoxin-TK for P/Q-type and omega-conotoxin-GVIA for N-type) revealed that, while N- and P/Q-type HVA Ca2+ channels are present in both MN pools, a 3.5-fold greater P/Q-type Ca2+ current in XII MNs accounts for their greater HVA Ca2+ currents. Developmentally, LVA and HVA Ca2+ current densities decrease in III MNs but remain unchanged in XII MNs. Thus, the differences between these MN pools increase developmentally so that, in juveniles, the LVA Ca2+ current density is twofold greater and the HVA Ca2+ current density is threefold greater in XII compared with III MNs. We propose that this differential expression of LVA and HVA Ca2+ channels in XII and III MNs during development contributes to their distinct physiology and may also be a factor contributing to the greater susceptibility of XII MNs to degeneration as seen in amyotrophic lateral sclerosis.

Postnatal development of persistent inward currents in rat XII motoneurons and their modulation by serotonin, muscarine and noradrenaline

“…For example, calcium channel involvement is unlikely since P‐ and Q‐type calcium currents in XII motoneurons do not change in the first 2 weeks (Miles et al . ), and the L‐type calcium current is small at best (undetected by Miles et al . ).…”

Postnatal Changes in the Inactivation Properties of Voltage-Gated Sodium Channels Contribute to the Mature Firing Pattern of Spinal Motoneurons

“…A possible explanation for this will be discussed in the following section but this finding suggests that, at least for the very early postnatal cells, the biophysical properties of the voltage-gated sodium current do not limit the maximal firing rates. Other mechanisms such as the low sodium current density (Gao and Ziskind-Conhaim 1998;Garcia et al 1998;McCobb et al 1990), or the underdeveloped potassium (McCobb et al 1990;Vinay et al 2000), or other conductances (McCobb et al 1989;Miles et al 2004;Mynlieff and Beam 1992) likely play a larger role in limiting the maximal firing rate at this stage of development.…”

“…This developmental phenomenon has been described in phrenic (Greer and Funk 2005;Martin-Caraballo and Greer 1999), oculomotor (Carrascal et al 2006), hypoglossal (Viana et al 1995), and spinal motoneurons (Fulton and Walton 1986;Vinay et al 2000;Vrbova et al 1985). This ability of motoneurons to discharge action potentials at an increasing rate has been attributed to various factors including an increase in sodium current density (Gao and Ziskind-Conhaim 1998;Garcia et al 1998;McCobb et al 1990), development of repolarizing conductances (McCobb et al 1990;Viana et al 1994;Vinay et al 2000), afterhyperpolarization amplitude increase (Fulton and Walton 1986), the development of calcium channels (McCobb et al 1989;Miles et al 2004;Mynlieff and Beam 1992), or changes in modulatory inputs (reviewed in Kernell 2003;Schmidt and Jordan 2000). In addition to an increase in firing frequency, a second defining characteristic of mature spinal motoneurons is their ability to generate plateau potentials (Perrier and Hounsgaard 2000).…”

Intrinsic properties of lumbar motor neurones in the adult G127insTGGG superoxide dismutase‐1 mutant mouse in vivo: evidence for increased persistent inward currents

“…2001). The ocular motor neurones also appear to have a lower density of voltage‐activated calcium currents than the more ALS vulnerable hypoglossal motor neurones (Miles et al. 2004).…”