The intracardiac ganglia (ICG) form the final common pathway for vagal innervation of the heart. Their location makes them susceptible to the effects of ischaemia and reperfusion associated with myocardial infarct. In other nervous system elements ischaemia results in impaired ATP production altering the electro-physiological responses of the neurones and causing disturbances in [Ca²⁺]_i homeostasis. During ischemia, [K⁺]_o can quickly accumulate to ~ 20 mM (Carmeliet 1999). Here we report the action of this disturbance on the electrophysiological properties of adult rat ICG neurones and their responses to nerve stimulation and exogenous acetylcholine (ACh). An isolated whole-mount preparation was used, comprising the right atrial ganglionic plexus primarily associated with control of sinoatrial node function (Sampaio et al. 2003). Intracellular recordings were made using sharp glass microelectrodes filled with Oregon Green 488 BAPTA-1 allowing simultaneous measurement of [Ca²⁺]_i. Signals resulting from [Ca²⁺]_i changes were expressed as the ratio of fluorescence changes over baseline fluorescence, (f-f_o)/f_o. Increasing K⁺ decreased membrane potential from -50.8 mV (± 5.7, S.D.) in 4.7 mM [K⁺]_o to -42.4 mV (± 4.5, n=10, p= 0.001, paired t-test) in 20 mM [K⁺]_o. The membrane resistance was also reduced from 6.2 (± 4.5) to 2.4 kΩ.cm² (± 1.4, n=10, p=0.001). The overshoot and afterhyperpolarization of somatic action potentials evoked by short (≤ 3 ms) current pulses were likewise significantly reduced in high K⁺. Antidromic axonal conduction was, however, insensitive to hyperkalemia. Synaptic transmission was investigated by applying trains of 20 stimuli at 5-100 Hz to the preganglionic nerve trunk. High [K⁺]_o attenuated postsynaptic action potential firing, inhibition was more marked at higher frequencies, 20 mM K⁺ practically blocked synaptic transmission in most neurones at all frequencies(n=5). Resting [Ca²⁺]_i was approximately 60 nM (± 29, n=12) in good agreement with previous reports for dissociated ICG neurones (Adams et al. 2003). [Ca²⁺]_i elevation could be evoked by somatic action potentials and focal application of ACh (100µM). A volley of 20 action potentials (10 Hz) increased [Ca²⁺]_i up to 1.5 times (f-f_o)/f_o (1.0±0.08, n=7), ACh resulted in comparable increases. High (20 mM) K⁺ had no consistent impact on resting [Ca²⁺]_i (n=8) and [Ca²⁺]_i transients evoked by direct action potential stimulation (n=6). Together, these results indicate that synaptic transmission in the ICG is susceptible to hyperkalemia. The electrical properties, resting [Ca²⁺]_i , action potential induced transients and axonal conduction are relatively insensitive. These data suggest that the presynaptic terminal is the principal target for hyperkalemia in ICG.