Raised extracellular potassium attenuates the sympathetic modulation of sino-atrial node pacemaking in the isolated guinea-pig atria.

Intense exercise or myocardial ischaemia can significantly increase both the concentration of extracellular potassium (K(+)) and cardiac sympathetic nerve activity. Since changes in K(+) modulate membrane currents involved in sino-atrial node pacemaking, in particular the voltage-sensitive hyperpolarization-activated current (I(f)), we investigated whether raised K(+) (from 4 mM to 8 or 12 mM) could directly affect the heart rate response to cardiac sympathetic nerve stimulation (SNS). In the isolated guinea-pig atrial-right stellate ganglion preparation, raised K(+) significantly decreased the maximum diastolic potential, amplitude and maximum rate of rise of the upstroke of sino-atrial node pacemaker action potentials in 8 and 12 mM K(+) (P < 0.05). At 12 mM K(+) these effects were associated with significant decreases in baseline heart rate (4 mM K(+) = 187 +/- 5 beats min(-1) (bpm); 12 mM = 144 +/- 11 bpm; P < 0.05) and the heart rate response to SNS (1, 3 and 5 Hz; P < 0.05). A 10 % increase in the baseline heart rate with sympathetic activation (3 Hz) was associated with a significant enhancement of the slope of the pacemaker diastolic depolarization at 4 mM K(+) (increased by 16 +/- 6 %; n = 7; P < 0.05), but not with raised K(+). When the I(f) current was blocked with 2 mM caesium (n = 8), 12 mM K(+) had no effect on baseline heart rate and the heart rate response to 3 Hz SNS. The heart rate response to bath-applied noradrenaline (0.01-100 microM) was significantly attenuated by 12 mM K(+) (at 4 mM K(+) EC(50) = -6.31 +/- 0.18; at 12 mM K(+) EC(50) = -5.80 +/- 0.10; n = 6, ANOVA, P < 0.05). In conclusion, extreme physiological levels of K(+) attenuate the positive chronotropic response to cardiac sympathetic activation due to decreased activation of the I(f) current. This is consistent with raised K(+) protecting the myocardium from potentially adverse effects of excessive noradrenaline. Experimental Physiology (2001) 86.1, 19-25.