Abnormal heart rate regulation in GIRK4 knockout mice

Kevin Wickman, Jan Nemec, Sandra J Gendler, David E. Clapham

Research output: Contribution to journalArticle

292 Citations (Scopus)

Abstract

Acetylcholine (ACh) released from the stimulated vagus nerve decreases heart rate via modulation of several types of ion channels expressed in cardiac pacemaker cells. Although the muscarinic-gated potassium channel I(KACH) has been implicated in vagally mediated heart rate regulation, questions concerning the extent of its contribution have remained unanswered. To assess the role of I(KACH) in heart rats regulation in vivo, we generated a mouse line deficient in I(KACH) by targeted disruption of the gene coding for GIRK4, one of the channel subunits. We analyzed heart rate and heart rate variability at rest and after pharmacological manipulation in unrestrained conscious mice using electrocardiogram (ECG) telemetry. We found that I(KACH) mediated approximately half of the negative chronotropic effects of vagal stimulation and adenosine on heart rate. In addition, this study indicates that I(KACH) is necessary for the fast fluctuations in heart rate responsible for beat-to-beat control of heart activity, both at rest and after vagal stimulation. Interestingly, noncholinergic systems also appear to modulate heart activity through I(KACH). Thus, I(KACH) is critical for effective heart rate regulation in mice.

Original languageEnglish (US)
Pages (from-to)103-114
Number of pages12
JournalNeuron
Volume20
Issue number1
DOIs
StatePublished - Jan 1998

Fingerprint

Knockout Mice
Heart Rate
Telemetry
Vagus Nerve
Potassium Channels
Ion Channels
Adenosine
Cholinergic Agents
Acetylcholine
Electrocardiography
Pharmacology
Genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Abnormal heart rate regulation in GIRK4 knockout mice. / Wickman, Kevin; Nemec, Jan; Gendler, Sandra J; Clapham, David E.

In: Neuron, Vol. 20, No. 1, 01.1998, p. 103-114.

Research output: Contribution to journalArticle

Wickman, Kevin ; Nemec, Jan ; Gendler, Sandra J ; Clapham, David E. / Abnormal heart rate regulation in GIRK4 knockout mice. In: Neuron. 1998 ; Vol. 20, No. 1. pp. 103-114.
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