If this is a Heritage with that funky "switch" to the left of the hammer, hmmmm...I've not shot a Heritage but I've handled them and that switch seemed damned unlikely to trip by accident. With the switch "up" (engaged) that hammer is totally blocked. So six-up would work.
Thing is though, if you left that safety off and treated the gun as a five-shooter, do the whole "load one, skip one, load four", first off it's a cross-trainer for a real Colt-type action and second, getting off the first shot is faster. Not that you're likely to have to treat a Heritage 22 as a defensive piece but...weirder things have happened. Any number of people in the field with a "plinker gun" have been confronted and have had to rely on same for defense without planning it out that way...