Efavirenz, atazanavir, and ritonavir disrupt sarcoplasmic reticulum Ca²⁺ homeostasis in skeletal muscles.

ABSTRACT: While muscle fatigue, pain and weakness are common co-morbidities in HIV-1 infected people, their underlying cause remain poorly defined. To this end, we evaluated whether the common antiretroviral drugs efavirenz (EFV), atazanavir (ATV) and ritonavir (RTV) could be a contributing factor by pertubating sarcoplasmic reticulum (SR) Ca²⁺ cycling. In live-cell imaging, EFV (6.0 μM), ATV (6.0 μM), and RTV (3.0 μM) elicited Ca²⁺ transients and blebbing of the plasma membranes of C2C12 skeletal muscle myotubes. Pretreating C2C12 skeletal muscle myotubes with the SR Ca²⁺ release channel blocker ryanodine (50 μM), slowed the rate and amplitude of Ca²⁺ release from and reuptake of Ca²⁺ into the SR. EFV, ATV and RTV (1 nM - 20 μM) potentiated and

SUBMITTER: Alomar FA 

PROVIDER: S-EPMC8019157 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature