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Ageing is associated with deterioration of calcium homeostasis in isolated human right atrial myocytes.

Herraiz-Martínez A, Álvarez-García J, Llach A, Molina CE, Fernandes J, Ferrero-Gregori A, Rodríguez C, Vallmitjana A, Benítez R, Padró JM, Martínez-González J, Cinca J, Hove-Madsen L - Cardiovasc. Res. (2015)

Bottom Line: Protein levels were determined by western blot.Ageing was associated with the following electrophysiological changes: (i) a 3.2-fold decrease in the calcium transient (P < 0.01); (ii) reduction of the L-type calcium current (ICa) amplitude (2.4 ± 0.3 pA/pF vs. 1.4 ± 0.2 pA/pF, P < 0.01); (iii) lower levels of L-type calcium channel alpha-subunit (P < 0.05); (iv) lower rates of both fast (14.5 ± 0.9 ms vs. 20.9 ± 1.9, P < 0.01) and slow (73 ± 3 vs. 120 ± 12 ms, P < 0.001) ICa inactivation; and (v) a decrease in the sarcoplasmic reticulum calcium content (10.1 ± 0.8 vs. 6.4 ± 0.6 amol/pF, P < 0.005) associated with a significant decrease in both SERCA2 (P < 0.05) and calsequestrin-2 (P < 0.05) protein levels.In contrast, ageing did not affect spontaneous sarcoplasmic reticulum calcium release.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Research Centre CSIC-ICCC and IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, St Antoni Mª Claret 167, Barcelona 08025, Spain.

No MeSH data available.


Related in: MedlinePlus

Effects of ageing on L-type calcium channel expression and current. (A) Representative L-type calcium currents elicited by depolarization to different membrane potentials (indicated above traces) in a young (20 years) and an old patient (77 years). (B) The ICa-voltage relationship in 21 young (<55) and 17 old (≥75) patients. (C) Peak ICa density in 21 young (<55), 42 middle aged (55–74), and 17 old (≥75) patients. (D) Western blot of the L-type calcium channel alpha subunit (DHPR) in seven young (<55 years), eight middle aged, and seven old (≥75 years) patients. Average DHPR levels are expressed as a percentage of the GAPDH level in the right panel. P-values for significant differences are indicated above the corresponding bars.
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CVV046F2: Effects of ageing on L-type calcium channel expression and current. (A) Representative L-type calcium currents elicited by depolarization to different membrane potentials (indicated above traces) in a young (20 years) and an old patient (77 years). (B) The ICa-voltage relationship in 21 young (<55) and 17 old (≥75) patients. (C) Peak ICa density in 21 young (<55), 42 middle aged (55–74), and 17 old (≥75) patients. (D) Western blot of the L-type calcium channel alpha subunit (DHPR) in seven young (<55 years), eight middle aged, and seven old (≥75 years) patients. Average DHPR levels are expressed as a percentage of the GAPDH level in the right panel. P-values for significant differences are indicated above the corresponding bars.

Mentions: To identify the mechanisms underlying the age-related depression of the calcium transient, we examined the effects of age on sarcolemmal calcium entry. Figure 2A shows recordings of ICa elicited at different membrane potentials in a young and an old patient demonstrating that ageing was associated with depressed ICa amplitude without changes in the shape of the current–voltage relationship (Figure 2B). Accordingly, continuous stimulation at 0.5 Hz revealed an age-dependent decrease in the ICa amplitude at steady state from 2.4 ± 0.3 pA/pF in young to 2.1 ± 0.2 pA/pF in middle aged and 1.4 ± 0.2 pA/pF in old patients (P < 0.001, young vs. old patients, Figure 2C). This effect was independent of confounding clinical factors included in the statistical analysis. Moreover, analysis of the data on a continuum confirmed that there is a significant correlation between age and the ICa density (r = 0.419; P < 0.001; see Supplementary material online, Figure S3). Western blot analysis revealed a concurrent age-related reduction in the expression of the L-type calcium channel alpha-subunits in patients (Figure 2D).Figure 2


Ageing is associated with deterioration of calcium homeostasis in isolated human right atrial myocytes.

Herraiz-Martínez A, Álvarez-García J, Llach A, Molina CE, Fernandes J, Ferrero-Gregori A, Rodríguez C, Vallmitjana A, Benítez R, Padró JM, Martínez-González J, Cinca J, Hove-Madsen L - Cardiovasc. Res. (2015)

Effects of ageing on L-type calcium channel expression and current. (A) Representative L-type calcium currents elicited by depolarization to different membrane potentials (indicated above traces) in a young (20 years) and an old patient (77 years). (B) The ICa-voltage relationship in 21 young (<55) and 17 old (≥75) patients. (C) Peak ICa density in 21 young (<55), 42 middle aged (55–74), and 17 old (≥75) patients. (D) Western blot of the L-type calcium channel alpha subunit (DHPR) in seven young (<55 years), eight middle aged, and seven old (≥75 years) patients. Average DHPR levels are expressed as a percentage of the GAPDH level in the right panel. P-values for significant differences are indicated above the corresponding bars.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4362404&req=5

CVV046F2: Effects of ageing on L-type calcium channel expression and current. (A) Representative L-type calcium currents elicited by depolarization to different membrane potentials (indicated above traces) in a young (20 years) and an old patient (77 years). (B) The ICa-voltage relationship in 21 young (<55) and 17 old (≥75) patients. (C) Peak ICa density in 21 young (<55), 42 middle aged (55–74), and 17 old (≥75) patients. (D) Western blot of the L-type calcium channel alpha subunit (DHPR) in seven young (<55 years), eight middle aged, and seven old (≥75 years) patients. Average DHPR levels are expressed as a percentage of the GAPDH level in the right panel. P-values for significant differences are indicated above the corresponding bars.
Mentions: To identify the mechanisms underlying the age-related depression of the calcium transient, we examined the effects of age on sarcolemmal calcium entry. Figure 2A shows recordings of ICa elicited at different membrane potentials in a young and an old patient demonstrating that ageing was associated with depressed ICa amplitude without changes in the shape of the current–voltage relationship (Figure 2B). Accordingly, continuous stimulation at 0.5 Hz revealed an age-dependent decrease in the ICa amplitude at steady state from 2.4 ± 0.3 pA/pF in young to 2.1 ± 0.2 pA/pF in middle aged and 1.4 ± 0.2 pA/pF in old patients (P < 0.001, young vs. old patients, Figure 2C). This effect was independent of confounding clinical factors included in the statistical analysis. Moreover, analysis of the data on a continuum confirmed that there is a significant correlation between age and the ICa density (r = 0.419; P < 0.001; see Supplementary material online, Figure S3). Western blot analysis revealed a concurrent age-related reduction in the expression of the L-type calcium channel alpha-subunits in patients (Figure 2D).Figure 2

Bottom Line: Protein levels were determined by western blot.Ageing was associated with the following electrophysiological changes: (i) a 3.2-fold decrease in the calcium transient (P < 0.01); (ii) reduction of the L-type calcium current (ICa) amplitude (2.4 ± 0.3 pA/pF vs. 1.4 ± 0.2 pA/pF, P < 0.01); (iii) lower levels of L-type calcium channel alpha-subunit (P < 0.05); (iv) lower rates of both fast (14.5 ± 0.9 ms vs. 20.9 ± 1.9, P < 0.01) and slow (73 ± 3 vs. 120 ± 12 ms, P < 0.001) ICa inactivation; and (v) a decrease in the sarcoplasmic reticulum calcium content (10.1 ± 0.8 vs. 6.4 ± 0.6 amol/pF, P < 0.005) associated with a significant decrease in both SERCA2 (P < 0.05) and calsequestrin-2 (P < 0.05) protein levels.In contrast, ageing did not affect spontaneous sarcoplasmic reticulum calcium release.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Research Centre CSIC-ICCC and IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, St Antoni Mª Claret 167, Barcelona 08025, Spain.

No MeSH data available.


Related in: MedlinePlus