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Voltage-activated calcium currents in octopus cells of the mouse cochlear nucleus.

ABSTRACT: Octopus cells, neurons in the most posterior and dorsal part of the mammalian ventral cochlear nucleus, convey the timing of synchronous firing of auditory nerve fibers to targets in the contralateral superior paraolivary nucleus and ventral nucleus of the lateral lemniscus. The low input resistances and short time constants at rest that arise from the partial activation of a large, low-voltage-activated K(+) conductance (g(KL)) and a large mixed-cation, hyperpolarization-activated conductance (g(h)) enable octopus cells to detect coincident firing of auditory nerve fibers with exceptional temporal precision. Octopus cells fire conventional, Na(+) action potentials but a voltage-sensitive Ca(2+) conductance was also detected. In this study, we explore the nature of that calcium conductance under voltage-clamp. Currents, carried by Ca(2+) or Ba(2+) and blocked by 0.4 mM Cd(2+), were activated by depolarizations positive to -50 mV and peaked at -23 mV. At -23 mV they reached 1.1 +/- 0.1 nA in the presence of 5 mM Ca(2+) and 1.6 +/- 0.1 nA in 5 mM Ba(2+). Ten micromolar BAY K 8644, an agonist of high-voltage-activated L-type channels, enhanced I(Ba) by 63 +/- 11% (n = 8) and 150 microM nifedipine, an antagonist of L-type channels, reduced the I(Ba) by 65 +/- 5% (n = 5). Meanwhile, 0.5 microM omega-Agatoxin IVA, an antagonist of P/Q-type channels, or 1 microM omega-conotoxin GVIA, an antagonist of N-type channels, suppressed I(Ba) by 15 +/- 4% (n = 5) and 9 +/- 4% (n = 5), respectively. On average 16% of the current remained in the presence of the cocktail of blockers, indicative of the presence of R-type channels. Together these experiments show that octopus cells have a depolarization-sensitive g(Ca) that is largely formed from L-type Ca(2+) channels and that P/Q-, N-, and R-type channels are expressed at lower levels in octopus cells.

SUBMITTER: Bal R

PROVIDER: S-EPMC2538346 | biostudies-other | 2007 Dec

REPOSITORIES: biostudies-other

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Project description:The importance and diversity of calcium signaling in the brain is mirrored by the expression of a multitude of voltage-activated calcium channel (Ca(V)) isoforms. Whereas the overall distributions of alpha(1) subunits are well established, the expression patterns of distinct channel isoforms in specific brain regions and neurons, as well as those of the auxiliary beta and alpha(2)delta subunits are still incompletely characterized. Further it is unknown whether neuronal differentiation and activity induce changes of Ca(V) subunit composition. Here we combined absolute and relative quantitative TaqMan reverse transcription PCR (RT-PCR) to analyze mRNA expression of all high voltage-activated Ca(V) alpha(1) subunits and all beta and alpha(2)delta subunits. This allowed for the first time the direct comparison of complete Ca(V) expression profiles of mouse cortex, hippocampus, cerebellum, and cultured hippocampal neurons. All brain regions expressed characteristic profiles of the full set of isoforms, except Ca(V)1.1 and Ca(V)1.4. In cortex development was accompanied by a general down regulation of alpha(1) and alpha(2)delta subunits and a shift from beta(1)/beta(3) to beta(2)/beta(4). The most abundant Ca(V) isoforms in cerebellum were Ca(V)2.1, beta(4), and alpha(2)delta-2, and in hippocampus Ca(V)2.3, beta(2), and alpha(2)delta-1. Interestingly, cultured hippocampal neurons also expressed the same Ca(V) complement as adult hippocampus. During differentiation specific Ca(V) isoforms experienced up- or down-regulation; however blocking electrical activity did not affect Ca(V) expression patterns. Correlation analysis of alpha(1), beta and alpha(2)delta subunit expression throughout all examined preparations revealed a strong preference of Ca(V)2.1 for beta(4) and alpha(2)delta-2 and vice versa, whereas the other alpha(1) isoforms were non-selectively expressed together with each of the other beta and alpha(2)delta isoforms. Together our results revealed a remarkably stable overall Ca(2+) channel complement as well as tissue specific differences in expression levels. Developmental changes are likely determined by an intrinsic program and not regulated by changes in neuronal activity.

Project description:Electrophysiological studies from mice in vitro have suggested that octopus cells of the mammalian ventral cochlear nucleus (VCN) are anatomically and biophysically specialized for detecting the coincident firing of a population of auditory nerve fibers. Recordings from cats in vivo have shown that octopus cells fire rapidly and with exceptional temporal precision as they convey the timing of that coincidence to higher auditory centers. The current study addresses the question whether the biophysical properties of octopus cells that have until now been examined only in mice, are shared by octopus cells in cats. Whole-cell patch-clamp recordings confirm that octopus cells in brain slices from kittens share the anatomical and biophysical features of octopus cells in mice. As in mice, octopus cells in kittens have large cell bodies and thick dendrites that extend in one direction. Voltage changes produced by depolarizing and hyperpolarizing current injection were small and rapid. Input resistances and membrane time constants in octopus cells of 16-day-old kittens were 15.8 +/- 1.5 MOmega (n = 16) and 1.28 +/- 0.3 ms (n = 16), respectively. Octopus cells fired only a single action potential at the onset of a depolarizing current pulse; suprathreshold stimuli were greater than 1.8 nA. A tetrodotoxin (TTX)-sensitive sodium conductance (gNa) was responsible for the generation of the action potentials. Octopus cells displayed outward rectification that lasted for the duration of the depolarizing pulses. Hyperpolarizations produced by the injection of current exhibited a depolarizing sag of the membrane potential toward the resting value. A 4-aminopyridine (4-AP) and alpha-dendrotoxin (alpha-DTX)-sensitive, low-voltage-activated potassium conductance (gKL) and a ZD7288-sensitive, mixed-cation conductance (gh) were partially activated at rest, giving the octopus cells low input resistances and, as a consequence, brief time constants. In 7-day-old kittens, action potentials were taller and broader, input resistances higher, and both inward and outward rectification was weaker than in 16-day-old kittens. Also as in mice, stellate cells of the VCN fired trains of action potentials with constant interspike intervals when they were depolarized (n = 10) and bushy cells of the VCN fired only a single action potential at the onset of depolarizations (n = 6). In conclusion, the similarity of octopus cells in mice and kittens suggests that the anatomical and biophysical specializations that allow octopus cells to detect and convey synchronous firing among auditory nerve fibers are common to all mammals.

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Voltage-activated calcium currents in octopus cells of the mouse cochlear nucleus.

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