There is increasing evidence that ubiquitous polyamines (PAs) are directly involved in modulating inactivation characteristics, or so-called "intrinsic gating", of outward current flowing through mouse and human hippocampal inwardly-rectifying K+ channels (IRKs) as expressed in Xenopus oocytes. As IRKs maintain resting membrane potential, block of these channels may lead to membrane depolarization and to subsequent increased excitability, possibly resulting in such phenomena as cardiac arrhythmias. The proposed research seeks to take such work and to analyze its physiological relevance in in vitro rat and human cardiac tissues, using i) biochemical quantitation of PAs, ii) biophysical analysis of IRK and PA interactions, and iii) molecular biological procedures to determine PA effects, if any, on IRK gene transcription as well as general IRK mRNA identification.