Table 3

Ryanodine receptor modulation: Functional classification

	Ca²⁺Release	γ	Po	K_D	Examples
Class I	increased or decreased^3-a	decreased	increased	—	ryanodine
Class II	increased	unchanged	increased^3-b	decreased	Ca²⁺ caffeine, MBED, sulmazole, doxorubicin adenine nucleotides, suramin
Class III	increased	unchanged	different from class II		halothane, heparin, bastadins
Class IV	decreased	unchanged	decreased^3-c	increased	Mg²⁺, ruthenium red, aminoglycosides, FLA 365
Class V	decreased	unchanged	different from class IV		procaine, tetracaine phenylalkylamines dantrolene
Class VI	decreased	decreased	unchanged	variable	spermine, QX 314
Class VII	— — — — — — — delayed persistent channel inactivation^3-d— — — — — —		doxorubicin, ruthenium red, neomycin

↵3-a Ryanodine has a double effect in release experiments, as detailed in the text.
↵3-b Due to decreased lifetime of the closed channel and/or increased lifetime of the open channel.
↵3-c Due to increased lifetime of the closed channel and/or decreased lifetime of the open channel.
↵3-d This action is produced after prolonged incubation with several agents whose immediate effect belongs to a different class.
γ, channel conductance; K_D , [³H]ryanodine dissociation constant.