The number of seats in the Senate varies after each election; as of 2014, the current Senate has 53 Democratic seats, 45 Republican seats and two Independent seats. This number can change during a term if senators change parties, retire or resign.
Senators hold their seats for six years at a time. Once those six years are up, they can opt to run for re-election. It is not guaranteed that a candidate will be renominated or win. The decision is left up to the voters the senator represents. If the voters do not like what the candidate is supporting or the work that was done in previous term, the senator will likely not be re-elected. This means his seat could go to someone of a different political party, which would change the party divisions.