CONTRIBUTION OF SHRINKAGE OF EXTRACELLULAR-SPACE TO EXTRACELLULAR K-ISCHEMIA OF THE RABBIT( ACCUMULATION IN MYOCARDIAL)

1. The contribution of the concentrating effect due to shrinkage of th e extracellular space (ECS) to cellular K+ efflux on extracellular pot assium ([K+](o)) accumulation in response to ischaemia was investigate d in an isolated, blood-perfused rabbit papillary muscle preparation w ith a confined extracellular space. 2. The ECS was quantified using ei ther of two extracellular markers, choline or tetramethyl ammonium (TM A), each with specific ion-selective electrodes, as well as by measure ment of extracellular resistance (r(o)). [K+](o) and [Na+](o) were als o measured simultaneously using K+- and Na+-selective electrodes. 3. D uring ischaemia, [K+](o) increased 3-fold from 4.2 +/- 0.1. to 12.6 +/ - 1.0 mM at 10 min (n = 10) analogous to changes in the ischaemic hear t in vivo. The ECS decreased to 83.9 +/- 3.2 % of control measured usi ng 1 mM choline extracellularly (n = 9, P < 0.01) or to 85.7 +/- 0.7 % of control using 1 mM TMA (n = 6, P < 0.01). Nearly identical decreas es in r(o)(84.1 +/- 2.4%, n = 15, P < 0.01) occurred simultaneously. 4 . The small decrease in the ECS contributed only 0.8-0.9 mM to the tot al increases in [K+](o) of 8.4 mM and had a minor effect on transmembr ane K+ flux. No significant differences between the relative changes i n [choline] and [Na+](o) were observed. This excluded a major transmem brane Na+ movement during early ischaemia. 5. Bumetanide (10 mM), an i nhibitor of K+-Cl- cotransport, a process which is involved in cell vo lume regulation consequent to osmotic cell swelling, significantly att enuated the increase in [K+](o) after 6 min of ischaemia (8.3 +/- 0.6 mM, n = 5 vs. 10.3 +/- 0.4 mM in the control group, n = 6, P < 0.05), whereas N-ethylmaleimide (1 mM), a stimulator of this cotransporter, a ugmented [K+](o) accumulation (12.0 +/- 0.6 mM at 6 min, P < 0.05). 6. We conclude that during early myocardial ischaemia, a major component of [K+](o) accumulation is not caused by diminution of ECS per se, bu t rather by increased net K+ efflux due in part to K+-Cl- cotransport secondary to myocyte volume regulation.