Modulation of Ca2+-gated cardiac muscle Ca2+-release channel (ryanodine receptor) by mono- and divalent ions

Wei Liu, Daniel A. Pasek, Gerhard Meissner
1998 American Journal of Physiology - Cell Physiology  
Modulation of Ca 2ϩ -gated cardiac muscle Ca 2ϩ -release channel (ryanodine receptor) by mono-and divalent ions. Am. J. Physiol. 274 (Cell Physiol. 43): C120-C128, 1998.-The effects of mono-and divalent ions on Ca 2ϩ -gated cardiac muscle Ca 2ϩ -release channel (ryanodine receptor) activity were examined in [ 3 H]ryanodine-binding measurements. Ca 2ϩ bound with the highest apparent affinity to Ca 2ϩ activation sites in choline chloride medium, followed by KCl, CsCl, NaCl, and LiCl media. The
more » ... LiCl media. The apparent Ca 2ϩ binding affinities of Ca 2ϩ inactivation sites were lower in choline chloride and CsCl media than in LiCl, NaCl, and KCl media. Sr 2ϩ activated the ryanodine receptor with a lower efficacy than Ca 2ϩ . Competition studies indicated that Li ϩ , K ϩ , Mg 2ϩ , and Ba 2ϩ compete with Ca 2ϩ for Ca 2ϩ activation sites. In 0.125 M KCl medium, the Ca 2ϩ dependence of [ 3 H]ryanodine binding was modified by 5 mM Mg 2ϩ and 5 mM ␤,␥-methyleneadenosine 5Јtriphosphate (a nonhydrolyzable ATP analog). The addition of 5 mM glutathione was without appreciable effect. Substitution of Cl Ϫ by 2-(N-morpholino)ethanesulfonic acid ion caused an increase in the apparent Ca 2ϩ affinity of the Ca 2ϩ inactivation sites, whereas an increase in KCl concentration had the opposite effect. These results suggest that cardiac muscle ryanodine receptor activity may be regulated by 1) competitive binding of mono-and divalent cations to Ca 2ϩ activation sites, 2) binding of monovalent cations to Ca 2ϩ inactivation sites, and 3) binding of anions to anion regulatory sites. sarcoplasmic reticulum
doi:10.1152/ajpcell.1998.274.1.c120 fatcat:bpvhgycvkze3fm3kzlnn2hs7xq