Effect of raised extracellular calcium on characteristics of the guinea-pig ventricular action potential.

The whole-cell patch-clamp method was used to investigate the role of Na/Ca exchange current (INa,Ca) in the shortening action of raised extracellular calcium on the ventricular action potential. Experiments were performed either using BAPTA to buffer intracellular calcium, or by replacing extracellular Na+ with Li- to abolish INa,Ca. A blocker of Ik, compound II. was used to investigate whether changes in this current may also play a role. Raising extracellular calcium from 1.8 mM to 5.0 mM increased the amplitude of the action potential by 8% and decreased its duration (at 90% repolarization, APD90) by 23%. Compound II increased APD90 by 40% and resulted in the appearance of early afterdepolarizations but did not affect the response to raised extracellular calcium. Intracellular BAPTA (20 mM) did not prevent the calcium-induced shortening but did abolish the initial rapid phase of repolarization and increase the inactivation time constant of Icsl recorded under voltage clamp. Replacement of extracellular Na+ with Li+ dramatically shortened the action potential and under these conditions raising extracellular calcium lengthened the action potential. Using a voltage-clamp protocol to mimic an action potential, whole-cell current in the absence and in the presence of Li(+)-replacement was recorded in normal and raised extracellular calcium. The lithium-sensitive current was inward during the "plateau" and was reduced by raising extracellular calcium. The results do not support a role for Ik in mediating action potential shortening in raised extracellular calcium. It is suggested that a decrease in inward INa,Ca may be largely responsible, with a role for increased Icsl inactivation in the early part of the action potential.