Regulation of dihydropyridine receptor levels in skeletal and cardiac muscle by exercise training

Abstract

To examine the influence of exercise training on the expression of dihydropyridine (DHP)-sensitive Ca2+ channels in skeletal and cardiac muscle, we have determined DHP receptor levels by [3H]PN200-110-binding and immunoblot analysis in homogenates and microsomal fractions of slow- and fast-twitch muscles and heart from rats subjected to a 12-week programme of moderate endurance training. We found that exercise increases the amount of DHP receptor in homogenates of the slow-twitch soleus (42%) and the fast-twitch extensor digitorum longus (60%). Comparable increases in DHP receptor density with training were also observed in the microsomal fractions isolated from both skeletal muscles; these increases were not due to differences in the membrane composition of the microsomal fractions, since the relative proportion of specific enzyme markers was not affected by exercise training. Levels of DHP receptor were not modified in cardiac muscle as a result of the exercise programme. These data suggest an up-regulation of the DHP receptor in the skeletal muscle as a consequence of exercise training, which may play a role in the adaptation of skeletal muscle to increased contractile activity.

Neural control of aging skeletal muscle

“…Whether excitation-contraction uncoupling results from alterations in neural control of muscle gene expression is not known at the present time. However, a series of studies have supported this concept: for example, denervation results in a significant decrease in DHPR functional expression and alterations in excitation-contraction coupling in skeletal muscle from adult rats (Delbono, 1992); nerve crush leads to reduction in the levels of mRNA encoding DHPR subunits and RyR1 in muscle (Ray et al ., 1995); also, there are indications that both DHPR and RyR1 expression are dependent on skeletal muscle innervation (Kyselovic et al ., 1994;Pereon et al ., 1997b); during development, DHPR mRNA levels change in relation with fibre innervation (Chaudari & Beam, 1993); myotube depolarization triggers the appearance of (+)-[ 3 H]PN 200 -110 binding sites (Pauwels et al ., 1987); and, finally, exercise and chronic stimulation in vivo increase the expression of DHPR in homogenates of soleus and EDL muscles (Saborido et al ., 1995;Pereon et al ., 1997a). These studies support the concept that fibre-type composition, DHPR and RyR1, and excitationcontraction coupling depend on nerve stimulation and muscle activity.…”

Overexpression of IGF-1 Exclusively in Skeletal Muscle Prevents Age-related Decline in the Number of Dihydropyridine Receptors

“…Therefore, an increase in contractile protein content in transgenic muscles does not account for the reported significant difference in tension. The expression of DHPR has been associated with skeletal muscle activity (30); it should be mentioned that transgenic and nontransgenic mice were housed in similar cages and exhibited similar physical activity. Although acute exposure to IGF-1 enhances calcium influx through DHPR (3), it is unlikely that potentiation of calcium influx plays a significant role during brief contractions of mouse skeletal muscle.…”

Measurement of Sarcoplasmic Reticulum Ca2+-ATPase Activity and E-Type Mg2+-ATPase Activity in Rat Heart Homogenates

“…When this cardiac mixed membrane fraction was employed to measure the SR Ca 2ϩ -ATPase activity, according to common procedures for skeletal muscle (17), an apparent negative value was obtained (Ϫ0.23 Ϯ 0.03 mol ⅐ min Ϫ1 ⅐ mg Ϫ1 ) since the basal activity, detected before the addition of 0.2 mM CaCl 2 and 4 M ionophore A23187, was higher than the total activity subsequently determined in the same cuvette after the addition of these compounds. Moreover, the initial descent in absorbance at 340 nm after the addition of ATP to the assay medium without Ca 2ϩ and ionophore was not linear, decreasing clearly with time (see below); therefore, the value of the basal ATPase activity was dependent on the time passed after the start of the reaction with ATP.…”