© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Stretch-dependent slow force response in isolated rabbit myocardium is Na+ dependent
aDepartment of Cardiology and Pneumology, Georg-August-University, Robert-Koch-Str. 40, 37075 Göttingen, Germany
bDepartment of Physiology, Loyola University, Chicago, IL, USA
pieske{at}med.uni-goettingen.de
* Corresponding author. Tel.: +49-551-398-925; fax: +49-551-391-9127.
Objective: Stretch induces functional and trophic effects in mammalian myocardium via various signal transduction pathways. We tested stretch signal transduction on immediate and slow force response (SFR) in rabbit myocardium. Methods: Experiments were performed in isolated right ventricular muscles from adult rabbit hearts (37 °C, 1 Hz stimulation rate, bicarbonate-buffer). Muscles were rapidly stretched from 88% of optimal length (L88) to near optimal length (L98) for functional analysis. The resulting immediate and slow increases in twitch force (first phase and SFR, respectively) were assessed at reduced [Na+]o or without and with blockade of stretch activated ion channels (SACs), angiotensin-II (AT1) receptors, endothelin-A (ETA) receptors, Na+/H+-exchange (NHE1), reverse mode Na+/Ca2+-exchange (NCX), or Na+/K+-ATPase. The effects of stretch on sarcoplasmic reticulum Ca2+-load were characterized using rapid cooling contractures (RCCs). Intracellular pH was measured in BCECF-AM loaded muscles, and action potential duration (APD) was assessed using floating electrodes. Results: On average, force increased to 216±8% of the pre-stretch value during the immediate phase, followed by a further increase to 273±10% during the SFR (n=81). RCCs significantly increased during SFR, whereas pH and APD did not change. Neither inhibition of SACs, AT1, or ETA receptors affected the stretch-dependent immediate phase nor SFR. In contrast, SFR was reduced by NHE inhibition and almost completely abolished by reduced [Na+]o or inhibition of reverse-mode NCX, whereas increased SFR was seen after raising [Na+]i by Na+/K+-ATPase inhibition. Conclusions: The data demonstrate the existence of a delayed, Na+- and Ca2+-dependent but pH and APD independent SFR to stretch in rabbit myocardium. This inotropic response appears to be independent of autocrine/paracrine AT1 or ETA receptor activation, but mediated through stretch-induced activation of NHE and reverse mode NCX.
KEYWORDS Ion exchangers; Signal transduction; Stretch/m-e coupling
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