This issue has been present for a long while, actually, and is related to how hotkeys are handled when there is a source selected in the sources list. Certain hotkeys will become disabled because they are reserved for shortcuts in that context in the program itself.
You can click on any other part of the application as long as it deselects a source from the sources list and hotkeys will work again.
Trust me when I say this annoys the heck out of me too, it's just not as simple of a fix as it requires quite a lot of reworking for how hotkeys currently function.