I am going on memory but I think the first ones were chambered in something like .577 caliber. They then necked it down to .450 using the same cartridge. They were definitely rifled. I have no idea when they were first chambered in .22 but the .22 rimfire (short) was the first modern cartridge, dating to the 1850's and the Smith and Wesson revolver.
The .22 versions btw worked very, very, well. You simply dropped the lever and tossed a cartridge on the huge loading platform. If you tilted the barrel down, the little .22 would find it's way into the chamber every time. Usually all you had to do then was raise the lever and the breech block cammed the cartridge all the way into the chamber. I could kick myself for trading it off.
The .22cal rimfire round was produced in the 1850's. See the Volcanic pistol for examples of it being used then.