Table 1.
Ca2+ sensitivity of tension
| Untreated (n = 13) | rAMPK:LKB1lo (n = 8) | rAMPK:LKB1hi (n = 6) | LKB1 (n = 6) | |
|---|---|---|---|---|
| EC50 (μM) | 2.58 ± 0.11 | 1.56 ±. 06∗ | 3.71 ± .17∗ | 4.16 ± .12∗ |
| pCa50 | 5.59 ± 0.02 | 5.81 ± 0.02∗ | 5.43 ± 0.02∗ | 5.38 ± 0.01∗ |
| Hill coefficient | 5.04 ± 0.44 | 5.31 ± 0.61 | 3.98 ± 0.58 | 6.97 ± 2.29 |
| ΔEC50 | 0.58 ± 0.10 | 0.59 ± 0.06 | 0.60 ± 0.17 | 0.43 ± 0.08 |
| ΔpCa50 | 0.08 ± 0.02 | 0.13 ± 0.04 | 0.07 ± 0.03 | 0.03 ± 0.01 |
| Maximum tension (mN/mm2) | 33.98 ± 2.32 (n = 36) | 35.33 ± 4.07 (n = 14) | 30.02 ± 2.62 (n = 18) | 21.50 ± 1.71∗ (n = 27) |
| Tension Redevelopment | ||||
|---|---|---|---|---|
| Untreated (n = 10) | rAMPK:LKB1lo (n = 12) | rAMPK:LKB1hi (n = 10) | LKB1 (n = 11) | |
| ktr max (s−1) | 5.28 ± 0.27 | 6.14 ± 0.41 | 4.91 ± 0.25 | 5.35 ± 0.54 |
| Linear fit (s−1/P/P0) | 4.19 ± 0.48 | 6.16 ± 0.71∗ | 5.08 ± 0.46 | 3.59 ± 0.37 |
| Monoexponential fit (s−1/P/P0) | 2.26 ± 0.59 | 10.02 ± 2.37∗ | 4.71 ± 0.73 | 3.96 ± 1.11 |
Each column contains mean values ± SE. Cardiac trabeculae were untreated or treated with low amounts of activating LKB1 complex to AMPK (rAMPK/LKB1lo), high amounts of activating LKB1 complex to AMPK (rAMPK:LKB1hi), or exogenous LKB1 complex alone (LKB1). The Ca2+ sensitivity of tension for each group is indicated by EC50 (μM) and pCa50. There is an increase in Ca2+ sensitivity in the rAMPK/LKB1lo group (p < 0.001). There is a decrease in Ca2+ sensitivity in the rAMPK/LKB1hi group (p < 0.001), and an even further decrease in Ca2+ sensitivity is seen with the LKB1 complex alone (p < 0.001). A one-way ANOVA indicated that all EC50 values were different from one another. There was no difference in cooperativity (Hill coefficient) or LDA (ΔEC50, ΔpCa50) between SLs of 2.2 μm and 2.0 μm. Maximum tension generation was also determined; LKB1 complex treatment decreased tension generation (p < 0.05). In an additional set of skinned fibers, the relationship between ktr and tension was determined with both a linear and monoexponential fit to the data. Slopes for each fit are reported above. There is an increase in the slope between ktr and tension in the rAMPK/LKB1lo group regardless of linear or monoexponential fit (p < 0.05) compared with untreated fibers. ∗, statistically significant difference.