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Vasomotion dynamics following calcium spiking depend on both cell signalling and limited constriction velocity in rat mesenteric small arteries.

VanBavel E, van der Meulen ET, Spaan JA - J. Cell. Mol. Med. (2008)

Bottom Line: The dirac impulse response of this model had an amplitude that was strongly reduced with increasing perfusion pressure between 17 and 98 mmHg, while time to peak and relaxation time were the largest at an intermediate pressure (57 mmHg: respectively 0.9 and 2.3 sec).In conclusion, this study demonstrates the feasibility of quantitating calcium-activation dynamics in vasomoting small arteries.Performing such analyses during pharmacological intervention and in genetic models provides a tool for unravelling calcium-contraction coupling in small arteries.

View Article: PubMed Central - PubMed

Affiliation: Academic Medical Center, University of Amsterdam, Department of Medical Physics, Amsterdam, The Netherlands. e.vanbavel@amc.uva.nl

ABSTRACT
Vascular smooth muscle cell contraction depends on intracellular calcium. However, calcium-contraction coupling involves a complex array of intracellular processes. Quantitating the dynamical relation between calcium perturbations and resulting changes in tone may help identifying these processes. We hypothesized that in small arteries accurate quantitation can be achieved during rhythmic vasomotion, and questioned whether these dynamics depend on intracellular signalling or physical vasoconstriction. We studied calcium-constriction dynamics in cannulated and pressurized rat mesenteric small arteries ( approximately 300 microm in diameter). Combined application of tetra-ethyl ammonium (TEA) and BayK8644 induced rhythmicity, consisting of regular and irregular calcium spiking and superposition of spikes. Calcium spikes induced delayed vasomotion cycles. Their dynamic relation could be fitted by a linear second-order model. The dirac impulse response of this model had an amplitude that was strongly reduced with increasing perfusion pressure between 17 and 98 mmHg, while time to peak and relaxation time were the largest at an intermediate pressure (57 mmHg: respectively 0.9 and 2.3 sec). To address to what extent these dynamics reside in intracellular signalling or vasoconstriction, we applied rhythmic increases in pressure counteracting the vasoconstriction. This revealed that calcium-activation coupling became faster when vasoconstriction was counteracted. During such compensation, a calcium impulse response remained that lasted 0.5 sec to peak activation, followed by a 1.0 sec relaxation time, attributable to signalling dynamics. In conclusion, this study demonstrates the feasibility of quantitating calcium-activation dynamics in vasomoting small arteries. These dynamics relate to both intracellular signalling and actual vasoconstriction. Performing such analyses during pharmacological intervention and in genetic models provides a tool for unravelling calcium-contraction coupling in small arteries.

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Illustration of the procedure for fitting linear first-order (A) and second-order (B) models (thinner lines) to the diameter response (thicker line) following the calcium signal (C). Inserts in (A) and (B) (right axes) denote the deviation between measurement and prediction. (D) and (E) depict the predicted diameter response for these first and second-order models to a hypothetic dirac pulse (F) in the calcium signal.
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fig04: Illustration of the procedure for fitting linear first-order (A) and second-order (B) models (thinner lines) to the diameter response (thicker line) following the calcium signal (C). Inserts in (A) and (B) (right axes) denote the deviation between measurement and prediction. (D) and (E) depict the predicted diameter response for these first and second-order models to a hypothetic dirac pulse (F) in the calcium signal.

Mentions: Figure 4A–C shows an example of fitting calcium-diameter relations based on the first-order model Iand second order model II to a 30 sec. period of oscillations. Figure 4C depicts the measured calcium sig-nal. Figure 4A indicates the measured diameter signal as well as the prediction by first-order dynamics, while Fig. 4B shows the fit to the second order model. Both latter panels also indicate the deviation between measured and predicted diameter. As can be seen, the fit to model I deviated substantially (r2= 0.830) and systematically from the signal, while the error was far less for the second order model II (r2= 0.962). The two fits were used to predict the response to a (hypothetic) calcium Dirac impulse (Fig. 4D–F). Such impulse responses characterize the properties of the calcium signalling and contractile machinery in the time domain. The first-order response (Fig. 4D) is by definition an immediate constriction followed by an exponential relaxation. For the second-order fit (Fig. 4E), a finite time elapses before peak constriction is reached. We fitted models I and II to 486 periods of around 30 sec vasomotion. Median r2 was 0.877 (quartiles 0.720–0.923) for model I, and 0.960 (quartiles 0.891–0.982) for model II. Considering the far tighter fit and less appearance of systematic deviations in model II, below the dynamic properties are only analyzed based on model II.


Vasomotion dynamics following calcium spiking depend on both cell signalling and limited constriction velocity in rat mesenteric small arteries.

VanBavel E, van der Meulen ET, Spaan JA - J. Cell. Mol. Med. (2008)

Illustration of the procedure for fitting linear first-order (A) and second-order (B) models (thinner lines) to the diameter response (thicker line) following the calcium signal (C). Inserts in (A) and (B) (right axes) denote the deviation between measurement and prediction. (D) and (E) depict the predicted diameter response for these first and second-order models to a hypothetic dirac pulse (F) in the calcium signal.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401133&req=5

fig04: Illustration of the procedure for fitting linear first-order (A) and second-order (B) models (thinner lines) to the diameter response (thicker line) following the calcium signal (C). Inserts in (A) and (B) (right axes) denote the deviation between measurement and prediction. (D) and (E) depict the predicted diameter response for these first and second-order models to a hypothetic dirac pulse (F) in the calcium signal.
Mentions: Figure 4A–C shows an example of fitting calcium-diameter relations based on the first-order model Iand second order model II to a 30 sec. period of oscillations. Figure 4C depicts the measured calcium sig-nal. Figure 4A indicates the measured diameter signal as well as the prediction by first-order dynamics, while Fig. 4B shows the fit to the second order model. Both latter panels also indicate the deviation between measured and predicted diameter. As can be seen, the fit to model I deviated substantially (r2= 0.830) and systematically from the signal, while the error was far less for the second order model II (r2= 0.962). The two fits were used to predict the response to a (hypothetic) calcium Dirac impulse (Fig. 4D–F). Such impulse responses characterize the properties of the calcium signalling and contractile machinery in the time domain. The first-order response (Fig. 4D) is by definition an immediate constriction followed by an exponential relaxation. For the second-order fit (Fig. 4E), a finite time elapses before peak constriction is reached. We fitted models I and II to 486 periods of around 30 sec vasomotion. Median r2 was 0.877 (quartiles 0.720–0.923) for model I, and 0.960 (quartiles 0.891–0.982) for model II. Considering the far tighter fit and less appearance of systematic deviations in model II, below the dynamic properties are only analyzed based on model II.

Bottom Line: The dirac impulse response of this model had an amplitude that was strongly reduced with increasing perfusion pressure between 17 and 98 mmHg, while time to peak and relaxation time were the largest at an intermediate pressure (57 mmHg: respectively 0.9 and 2.3 sec).In conclusion, this study demonstrates the feasibility of quantitating calcium-activation dynamics in vasomoting small arteries.Performing such analyses during pharmacological intervention and in genetic models provides a tool for unravelling calcium-contraction coupling in small arteries.

View Article: PubMed Central - PubMed

Affiliation: Academic Medical Center, University of Amsterdam, Department of Medical Physics, Amsterdam, The Netherlands. e.vanbavel@amc.uva.nl

ABSTRACT
Vascular smooth muscle cell contraction depends on intracellular calcium. However, calcium-contraction coupling involves a complex array of intracellular processes. Quantitating the dynamical relation between calcium perturbations and resulting changes in tone may help identifying these processes. We hypothesized that in small arteries accurate quantitation can be achieved during rhythmic vasomotion, and questioned whether these dynamics depend on intracellular signalling or physical vasoconstriction. We studied calcium-constriction dynamics in cannulated and pressurized rat mesenteric small arteries ( approximately 300 microm in diameter). Combined application of tetra-ethyl ammonium (TEA) and BayK8644 induced rhythmicity, consisting of regular and irregular calcium spiking and superposition of spikes. Calcium spikes induced delayed vasomotion cycles. Their dynamic relation could be fitted by a linear second-order model. The dirac impulse response of this model had an amplitude that was strongly reduced with increasing perfusion pressure between 17 and 98 mmHg, while time to peak and relaxation time were the largest at an intermediate pressure (57 mmHg: respectively 0.9 and 2.3 sec). To address to what extent these dynamics reside in intracellular signalling or vasoconstriction, we applied rhythmic increases in pressure counteracting the vasoconstriction. This revealed that calcium-activation coupling became faster when vasoconstriction was counteracted. During such compensation, a calcium impulse response remained that lasted 0.5 sec to peak activation, followed by a 1.0 sec relaxation time, attributable to signalling dynamics. In conclusion, this study demonstrates the feasibility of quantitating calcium-activation dynamics in vasomoting small arteries. These dynamics relate to both intracellular signalling and actual vasoconstriction. Performing such analyses during pharmacological intervention and in genetic models provides a tool for unravelling calcium-contraction coupling in small arteries.

Show MeSH
Related in: MedlinePlus