Questions about Adaptation in Ryanodine Receptors

“Inactivation” and “desensitization” are names traditionally used to describe refractory behavior in voltage- and ligand-gated channels, respectively. Laver and Lamb 1998 found that two RyR phenomena arise out of one inactivation mechanism: (1) the channel becomes refractory to the continued presence of a stimulatory ligand (i.e., desensitization); and (2) the channel activity declines after a voltage-step (inactivation). Thus, both terms (“desensitization” and “inactivation”) could be used to describe the one mechanism depending on how it is observed (ligand-step or voltage-step). Although RyRs are gated by both voltage and by ligands, “inactivation” has generally been adopted as the term to describe refractory closing of RyRs. Inactivation appears as long closed periods that separate spontaneous bursts of activity. During a closed period, the RyR cannot be activated by raising the ligand concentration but can be reactivated immediately by changing the voltage (see Figure 10 in Laver and Lamb 1998).