Don't underestimate the effectiveness of the lowly .22.  I carryed a .22 for many years while fishing from a tube.  I have killed many BIG snakes with it, some may have required more than one shot, but in the end they were dead.
I picked the .22 because I found a cheap (ROHM cost $25-$30) Saturday night special that I could leave in one of the compartments in the tube, and didn't mind getting wet, or a little rust on the gun, and wouldn't cry if someone releived me of it.  The little gun never failed me over almost 30 years.
Today, I don't tube fish anymore, and my choice is the .38, I loaded up a hundred round of shotshell several years ago, and am still shooting them out of my model 60.  I have killed several really big rattlesnakes with them.  I think it is about as cheap to buy ready rolled as to reload today.