Nitric Oxide Protects L-Type Calcium Channel of Cardiomyocyte during Long-Term Isoproterenol Stimulation in Tail-Suspended Rats

Abstract EN

The aim of this study was to investigate the effects of nitric oxide (NO) and reactive oxygen species (ROS) on L-type calcium channel (LTCC) gating properties of cardiomyocytes during long-term isoproterenol (ISO) stimulation.

Expression and activity of nNOS as well as S-nitrosylation of LTCC α1C subunit significantly decreased in the myocardium of SUS rats.

Long-term ISO stimulation increased ROS in cardiomyocytes of SUS rats.

ISO-enhanced calcium current (ICa,L) in the SUS group was less than that in the CON group.

The maximal ICa,L decreased to about 80% or 60% of initial value at the 50th minute of ISO treatment in CON or SUS group, respectively.

Specific inhibitor NAAN of nNOS reduced maximal ICa,L to 50% of initial value in the CON group; in contrast, NO donor SNAP maintained maximal ICa,L in SUS group to similar extent of CON group after 50 min of ISO treatment.

Long-term ISO stimulation also changed steady-state activation (P<0.01), inactivation (P<0.01), and recovery (P<0.05) characteristics of LTCC in SUS group.

In conclusion, NO-induced S-nitrosylation of LTCC α1C subunit may competitively prevent oxidation from ROS at the same sites.

Furthermore, LTCC can be protected by NO during long-term ISO stimulation.