Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we will assume that you are happy to receive all cookies and you will not see this message again. Click 'Find out more' for information on how to change your cookie settings.

Intense exercise or myocardial ischaemia can significantly increase both the concentration of extracellular potassium ([K(+)](o)) and cardiac sympathetic nerve activity. Since changes in [K(+)](o) modulate membrane currents involved in sino-atrial node pacemaking, in particular the voltage-sensitive hyperpolarization-activated current (I(f)), we investigated whether raised [K(+)](o) (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(+)](o) 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(+)](o) (P < 0.05). At 12 mM [K(+)](o) these effects were associated with significant decreases in baseline heart rate (4 mM [K(+)](o) = 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(+)](o) (increased by 16 +/- 6 %; n = 7; P < 0.05), but not with raised [K(+)](o). When the I(f) current was blocked with 2 mM caesium (n = 8), 12 mM [K(+)](o) 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(+)](o) (at 4 mM [K(+)](o,) EC(50) = -6.31 +/- 0.18; at 12 mM [K(+)](o,) EC(50) = -5.80 +/- 0.10; n = 6, ANOVA, P < 0.05). In conclusion, extreme physiological levels of [K(+)](o) attenuate the positive chronotropic response to cardiac sympathetic activation due to decreased activation of the I(f) current. This is consistent with raised [K(+)](o) protecting the myocardium from potentially adverse effects of excessive noradrenaline. Experimental Physiology (2001) 86.1, 19-25.

Type

Journal article

Journal

Exp Physiol

Publication Date

01/2001

Volume

86

Pages

19 - 25

Keywords

Action Potentials, Animals, Atrial Function, Cesium, Electric Stimulation, Extracellular Space, Guinea Pigs, Heart Conduction System, Heart Rate, In Vitro Techniques, Male, Norepinephrine, Potassium, Sinoatrial Node, Sympathetic Nervous System