QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, December 8, 2004, 24(49):11079-11087; doi:10.1523/JNEUROSCI.2713-04.2004

This Article Full Text Full Text (PDF) A correction has been published Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Cui, G. Articles by Morikawa, H. Search for Related Content PubMed PubMed Citation Articles by Cui, G. Articles by Morikawa, H.

 Previous Article  |  Next Article 

Cellular/Molecular
Spontaneous Opening of T-Type Ca²⁺ Channels Contributes to the Irregular Firing of Dopamine Neurons in Neonatal Rats

Guohong Cui, Takashi Okamoto, and Hitoshi Morikawa

Waggoner Center for Alcohol and Addiction Research, Section of Neurobiology and Institute for Neuroscience, University of Texas, Austin, Texas 78712

During early postnatal development, midbrain dopamine (DA) neurons display anomalous firing patterns and amphetamine response. Spontaneous miniature hyperpolarizations (SMHs) are observed in DA neurons during the same period but not in adults. These hyperpolarizations have been shown to be dependent on the release of Ca²⁺ from internal stores and the subsequent activation of Ca²⁺-sensitive K⁺ channels. However, the triggering mechanism and the functional significance of SMHs remain poorly understood. To address these issues, using brain slices, we recorded spontaneous miniature outward currents (SMOCs) in DA neurons of neonatal rats. Two types of SMOCs were identified based on the peak amplitude. Both types were suppressed by intracellular dialysis of ruthenium red, a ryanodine receptor (RyR) antagonist, yet none of the known Ca²⁺-releasing messengers were involved. T-type Ca²⁺ channel blockers (Ni²⁺ and mibefradil) inhibited large-amplitude SMOCs without affecting the small-amplitude ones. The voltage dependence of SMOCs displayed a peak of approximately -50 mV, consistent with the involvement of low-threshold T-type Ca²⁺ channels. Blockade of SMOCs with cyclopiazonic acid or ryanodine converted the irregular firing of DA neurons in neonatal rats into an adult-like pacemaker pattern. This effect was reversed by the injection of artificial currents mimicking SMOCs. Finally, amphetamine inhibited SMOCs and transformed the irregular firing pattern into a more regular one. These data demonstrate that Ca²⁺ influx through T-type Ca²⁺ channels, followed by Ca²⁺-induced Ca²⁺ release via RyRs, contributes to the generation of SMOCs. We propose that SMOCs-SMHs may underlie the anomalous firing and amphetamine response of DA neurons during the postnatal developmental period.

Key words: intracellular Ca²⁺ signaling; T-type Ca²⁺ channels; SK channels; ryanodine receptors; dopamine neurons; firing pattern

---

Received July 7, 2004; revised October 1, 2004; accepted October 20, 2004.

This article has been cited by other articles:

				A. Sarihi, B. Jiang, A. Komaki, K. Sohya, Y. Yanagawa, and T. Tsumoto Metabotropic Glutamate Receptor Type 5-Dependent Long-Term Potentiation of Excitatory Synapses on Fast-Spiking GABAergic Neurons in Mouse Visual Cortex J. Neurosci., January 30, 2008; 28(5): 1224 - 1235. [Abstract] [Full Text] [PDF]

				G. Cui, B. E. Bernier, M. T. Harnett, and H. Morikawa Differential Regulation of Action Potential- and Metabotropic Glutamate Receptor-Induced Ca2+ Signals by Inositol 1,4,5-Trisphosphate in Dopaminergic Neurons J. Neurosci., April 25, 2007; 27(17): 4776 - 4785. [Abstract] [Full Text] [PDF]

				Y. Yanovsky, S. Velte, and U. Misgeld Ca2+ release-dependent hyperpolarizations modulate the firing pattern of juvenile GABA neurons in mouse substantia nigra pars reticulata in vitro J. Physiol., December 15, 2006; 577(3): 879 - 890. [Abstract] [Full Text] [PDF]

				L. Zhang, Y. Liu, and X. Chen Carbachol induces burst firing of dopamine cells in the ventral tegmental area by promoting calcium entry through L-type channels in the rat J. Physiol., October 15, 2005; 568(2): 469 - 481. [Abstract] [Full Text] [PDF]

				T. A. Richter, M. Kolaj, and L. P. Renaud Low Voltage-Activated Ca2+ Channels Are Coupled to Ca2+-Induced Ca2+ Release in Rat Thalamic Midline Neurons J. Neurosci., September 7, 2005; 25(36): 8267 - 8271. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help