- Meeting abstract
- Open Access
2091 Manganese enhanced mri demonstrates a predominant role for nNOS, not eNOS, in modulating L-Type calcium channel flux in the heart
© Vandsburger et al; licensee BioMed Central Ltd. 2008
- Published: 22 October 2008
- Nitric Oxide
- Calcium Release
- Axis Slice
- Short Axis Slice
- Recovery Sequence
Modulation of L-Type Calcium Channel (LTCC) flux plays an important role in calcium cycling and contractility. Based upon localization within the cardiomyocyte, prevailing opinion is that neuronal nitric oxide synthase (nNOS) modulates sarcoplasmic reticular calcium release, while endothelial NOS (eNOS) modulates LTCC flux. Counter to this hypothesis, a recent in vitro study suggests that nNOS modulates LTCC flux. Since Mn2+ enters the myocyte through the LTCC in proportion to Ca2+ flux and shortens T1, Mn-enhanced MRI may be used to probe in vivo LTCC flux.
Higher BP was found in eNOS-/- mice compared to nNOS-/- (106 ± 4 WT, 111 ± 4 eNOS-/-, 94 ± 3 nNOS-/- p = 0.01 vs. eNOS-/-). Heart rate was similar between all groups (481 ± 18 WT, 470 ± 16 eNOS-/-, 490 ± 29 nNOS-/-, P = NS). LTCCI trended higher in eNOS-/- compared to WT (P = 0.1), but was nearly twice the WT rate in nNOS-/- mice (P < 0.001) (Figure 1). Additionally, LTTCI was significantly greater in nNOS-/- compared to eNOS-/- mice (P < 0.05).
The significantly increased rate of Mn2+ enhancement in nNOS-/- mice represents the first in vivo evidence of modulation of LTCC flux by nNOS. Although eNOS-/- mice showed a trend towards a higher rate of LTCC flux compared to WT, this increase is likely a response to heightened afterload. The absence of heightened BP in nNOS-/- mice paired with an increased LTCCI demonstrates that nNOS, not eNOS, plays a dominant role in modulating LTCC flux.
This article is published under license to BioMed Central Ltd.