Abstract
The multifunctional Ca2+/calmodulin-dependent kinase II (CaMKII) is activated by vasoconstrictors in vascular smooth muscle cells (VSMC), but its impact on vasoconstriction remains unknown. We hypothesized that CaMKII inhibition in VSMC decreases vasoconstriction. Using novel transgenic mice that express the inhibitor peptide CaMKIIN in smooth muscle (TG SM-CaMKIIN), we investigated the effect of CaMKII inhibition on L-type Ca channel current (ICa), cytoplasmic and sarcoplasmic reticulum Ca2+, and vasoconstriction in mesenteric arteries. In mesenteric VSMC, CaMKII inhibition significantly reduced action potential duration and the residual ICa 50 ms after peak amplitude, indicative of loss of L-type Ca2+ channel-dependent ICa facilitation. Treatment with angiotensin II or phenylephrine increased the intracellular Ca2+ concentration in wild-type but not TG SM-CaMKIIN VSMC. The difference in intracellular Ca 2+ concentration was abolished by pretreatment with nifedipine, an L-type Ca2+ channel antagonist. In TG SM-CaMKIIN VSMC, the total sarcoplasmic reticulum Ca2+ content was reduced as a result of diminished sarcoplasmic reticulum Ca2+ ATPase activity via impaired derepression of the sarcoplasmic reticulum Ca2+ ATPase inhibitor phospholamban. Despite the differences in intracellular Ca 2+concentration, CaMKII inhibition did not alter myogenic tone or vasoconstriction of mesenteric arteries in response to KCl, angiotensin II, and phenylephrine. However, it increased myosin light chain kinase activity. These data suggest that CaMKII activity maintains intracellular calcium homeostasis but is not required for vasoconstriction of mesenteric arteries.
Original language | English (US) |
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Pages (from-to) | 434-441 |
Number of pages | 8 |
Journal | Hypertension |
Volume | 62 |
Issue number | 2 |
DOIs | |
State | Published - Aug 2013 |
Externally published | Yes |
Keywords
- Ca/calmodulin-dependent protein kinase type 2-Calcium signaling
- L-type Ca channel
- Myometrial contraction
ASJC Scopus subject areas
- Internal Medicine