Ratio of ryanodine to dihydropyridine receptors in cardiac and skeletal muscle and implications for E-C coupling

We measured dihydropyridine receptor (DHPR) and ryanodine receptor (RYR) density in isolated ventricular myocytes from rabbits, rats, ferrets, and guinea pigs and also from rabbit ventricular homogenate, skeletal muscle homogenate, and isolated triads. In skeletal muscle homogenate and triads the RYR/DHPR ratio was 0.7 and 0.52, respectively. This stoichiometry is reasonably consistent with excitation-contraction (E-C) coupling models in skeletal muscle where the DHPR molecule itself may transmit the signal for Ca release to the sarcoplasmic reticulum (SR) and with the molecular arrangement proposed for toadfish swimbladder from ultrastructural studies by B. A. Block, T. Imagawa, K. P. Campbell, and C. Franzini-Armstrong. (J. Cell Biol. 107: 2587-2600, 1988). That is, there could be approximately two RYR for each four DHPR or two RYR feet per DHPR tetrad in an organized array (assuming 1 high-affinity RYR/foot and 4 DHPR/tetrad). The fraction of rabbit ventricular protein that is cardiac myocyte protein was also estimated (< or = 55-62%), assuming that RYR and DHPR are useful but not exclusive markers for myocytes in the ventricle. In cardiac myocytes the RYR/DHPR was much higher than in skeletal muscle and varied among different mammalian myocytes. The RYR/DHPR ratios were 3.7 in rabbit, 4.3 in guinea pig, 7.3 in rat, and 10.2 in ferret myocytes. In contrast to skeletal muscle, these results indicate that there are many more RYR feet per DHPR in cardiac muscle, and this ratio depends on species (i.e., 4-10 times and would be 4 times higher still per putative DHPR tetrad if that structure exists in mammalian heart).(ABSTRACT TRUNCATED AT 250 WORDS)