Chronic ethanol drinking reduces native T-type calcium current in the thalamus of nonhuman primates

W. Breckinridge Carden, Georgia M. Alexander, David P. Friedman, James B. Daunais, Kathleen A. Grant, Jian Mu, Dwayne W. Godwin

    Research output: Contribution to journalArticle

    19 Scopus citations

    Abstract

    Background: Chronic ethanol use is known to disrupt normal sleep rhythms, but the cellular basis for this disruption is unknown. An important contributor to normal sleep patterns is a low-threshold calcium current mediated by T-type calcium channels. The T-type calcium current underlies burst responses in thalamic nuclei that are important to spindle propagation, and we recently observed that this current is sensitive to acute low doses of ethanol. Methods:We used a combination of current clamp and voltage clamp recordings in an in vitro brain slice preparation of the dorsal lateral geniculate nucleus (LGN) of macaque monkeys that have chronically self-administered ethanol to determine whether chronic ethanol exposure may affect T-type currents. Results:Current clamp recordings from the LGN of ethanol naive macaques showed characteristic burst responses. However, recordings from the LGN in macaques that self-administered ethanol revealed a significant attenuation of bursts across a range of voltages (n = 5). Voltage clamp recordings from control LGN neurons (n = 16) and neurons (n = 29) from brain slices from chronically drinking macaques showed no significant differences (P > 0.05) in T-type current kinetics or in the membrane resistance of the thalamic cells between the two cohorts. However, mean T-type current amplitude measured in the chronically drinking animals was reduced by 31% (P < 0.01). Conclusions:We conclude that chronic ethanol self-administration reduces calcium currents in thalamic relay cells without altering underlying current kinetics, which may provide a mechanistic framework for the well-documented disruptions in sleep/wake behavior in subjects with chronic ethanol exposure.

    Original languageEnglish (US)
    Pages (from-to)92-100
    Number of pages9
    JournalBrain research
    Volume1089
    Issue number1
    DOIs
    StatePublished - May 17 2006

    Keywords

    • Alcoholism
    • Burst
    • Cynomolgus macaque
    • In vitro
    • Sleep

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Molecular Biology
    • Clinical Neurology
    • Developmental Biology

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