Table 2

Pharmacological modulators

Ca2+ releaseSingle channel[3H]Ryanodine binding
γPoAffinity (1/KD )Bmax
Ryanodine+/−2-a −2-a +2-a
Methylxanthines (e.g. caffeine)+0+++
MBED+0+++
4,6-dibromo-3-hyroxycarbazole−ndnd00
Sulmazole+0++0
Anthraquinones (e.g., doxorubicin)+/−2-a 02-a +/−2-a +0/−2-a
Digoxin+2-b 0+2-b ndnd
Milrinone+0+   +
Suramin+0+++
Halothane+0+0+bc
Enflurane+0+0(+)bd
Isoflurane+0(+)0(+)ed
4-chloro-m-cresol+0++0
δ-Hexachlorocyclohexane+ndnd(+)−
FK-506+−+0−
Rapamycin+−+0−
Bastadin 5+2-e 0+ef +2-e +ec
Quinolidomicin A1+ndnd+0
Heparin+0+002-g
Ruthenium red−2-a 0−2-a −2-a −2-a
Aminoglycosides (e.g., neomycin)−2-a 0−2-a −2-a −2-a
FLA365−0−−−
Dantrolene−0+/−2-h −0
Tetracaine−02-i −0−
Procaine−02-i −   −
Lidocaine−ndnd+0
QX 314−−0+0
Verapamil/gallopamil2-j −0−002-c
Buthotus hottentota venomnd−+++
Imperatoxin-a+2-e 0+2-e 0+2-e
Imperatoxin-i−0−   −
Miotoxin a+ndnd00
Helotherminend0−   −
Ryanotoxin+−++0
Thimerosal+0+/−2-k 0   −
Dithiodipyridine+ndnd   −2-l
Hydrogen peroxide+/−2-a 02-a +/−2-a ++/−2-a
TMPyP+0+++
Disulfonic stilbene derivatives+0+ndnd
Dicyclohexylcarbodiimide−ndnd   −
Fluorescin-5′-isothiocyanidend−+0−
Diethylpyrocarbonate+ndnd0−

  • Summary of the effects of pharmacological modulators in Ca2+ release, single-channel and [3H]ryanodine binding experiments. Only the most representative modulators are included in the table. In particular, substances whose action is controversial or incompletely characterized are omitted. See text for further details. Effects onKD and Bmax could not be distinguished in some cases.

  • ↵2-a Prolonged exposure to high concentrations determined persistent channel inactivation with reduced ryanodine binding.

  • ↵2-b An effect was produced selectively in cardiac muscle.

  • ↵2-c Low affinity ryanodine binding was reduced.

  • 2-d In cardiac tissue, low-affinity binding was increased.

  • ↵2-e An effect was produced selectively in skeletal muscle.

  • 2-f Both open and closed states were stabilized, the net effect being a slight increase in channel Po.

  • ↵2-g Ryanodine binding may be increased at very high heparin concentrations.

  • ↵2-h Controversial findings have been reported, and the effect might be biphasic.

  • ↵2-i Conductance may be reduced at high concentrations.

  • ↵2-j Ca2+ release and single-channel results were obtained with verapamil; modulation of low-affinity binding was studied with gallopamil.

  • ↵2-k Channel Po was increased at low concentrations and decreased at high concentrations.

  • ↵2-l Ryanodine binding was slightly stimulated at low concentrations.

  • γ, channel conductance; +, increased; (+), increase has not been consistently reported; −, decreased; 0, unchanged; nd, not determined.