The effect of natural polyamines on KATP channels was studied using inside-out patches from guinea-pig ventricular myocytes. 2. At a holding potential of +40 mV, spermine at the intracellular membrane surface reduced the KATP channel open probability (Popen) in a dose-dependent manner. Half-maximal inhibition occurred at 29 microM with a Hill coefficient of 1.2. 3. The effect of spermine on Popen was not greatly influenced by the membrane potential but there appeared to be a small reduction in unitary current amplitude during strong depolarizations. 4. Analysis of KATP single channel kinetics showed that spermine inhibited the channel by decreasing the mean open time and introducing transitions to a long closed state. 5. Spermidine (0.1 mM) was found to have a similar effect to spermine. Putrescine (10 mM) was found to block more effectively at positive membrane potentials. Up to 20 mM arginine had no significant effect on KATP channels. 6. Our results indicate that natural polyamines influence native KATP channel gating in cardiac myocytes.
