We establish the following sufficient operator-theoretic condition for a subspace S ⊂ L 2 (R, dν) to be a reproducing kernel Hilbert space with the Kramer sampling property. If the compression of the unitary group U (t) := e it M generated by the self-adjoint operator M, of multiplication by the independent variable, to S is a semigroup for t ≥ 0, if M has a densely defined, symmetric, simple and regular restriction to S, with deficiency indices (1, 1), and if ν belongs to a suitable large class of Borel measures, then S must be a reproducing kernel Hilbert space with the Kramer sampling property. Furthermore, there is an isometry which acts as multiplication by a measurable function which takes S onto a reproducing kernel Hilbert space of functions which are analytic in a region containing R, and are meromorphic in C. In the process of establishing this result, several new results on the spectra and spectral representations of symmetric operators are proven. It is further observed that there is a large class of de Branges functions E, for which the de Branges spaces