Role of Neuronal KATP Channels and Extraneuronal Monoamine Transporter on Norepinephrine Overflow in a Model of Myocardial Low Flow Ischemia

Christof Burgdorf*, Andreas Dendorfer, Thomas Kurz, Edgar Schömig, Ines Stölting, Frank Schütte, Gert Richardt

*Corresponding author for this work
26 Citations (Scopus)

Abstract

Global myocardial low flow ischemia results in an uniform suppression of norepinephrine (NE) overflow from the heart. We hypothesized that opening of neuronal ATP-sensitive potassium (KATP) channels as well as activation of the extraneuronal monoamine transporter (EMT) mediates attenuation of NE overflow during low flow ischemia. Isolated rat hearts were subjected to low coronary flow of 0.4 ml min-1. Release of endogenous NE was induced by electrical field stimulation. EMT activity was measured as the transport rate of the substrate N-[methyl- 3H]4-phenylpyridinium ([3H]MPP+). NE overflow decreased by 57 ± 2% within 120 min of low flow. Five minutes of reperfusion at normal flow (8 ml min-1) restored NE overflow to baseline. KATP channel blockade with glibenclamide as well as EMT blockade with corticosterone increased NE overflow 1.5- and 2-fold at 120 min of low flow, whereas neither drug affected NE overflow in the absence of flow reduction. At normal flow, KATP channel opening with cromakalim suppressed NE overflow, both in the presence and absence of EMT blockade (14 ± 4 and 9 ± 1%). However, cromakalim had no effect on EMT activity as indicated by an unaffected [3H]MPP+ overflow. In conclusion, activation of both KATP channels and EMT mediate suppression of NE overflow during low flow ischemia. KATP channels impair NE release directly at presynaptic nerve endings, whereas EMT increases NE elimination in a manner independent of KATP channels.

Original languageEnglish
JournalJournal of Pharmacology and Experimental Therapeutics
Volume309
Issue number1
Pages (from-to)42-48
Number of pages7
ISSN0022-3565
DOIs
Publication statusPublished - 01.01.2004

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

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