ASYMMETRIC MODULATION AND BLOCKADE OF THE DELAYED RECTIFIER IN SQUID GIANT-AXONS BY DIVALENT-CATIONS

The effects of intracellular magnesium ions and extracellular calcium and magnesium ions on the delayed rectifier potassium ion channel, I-K , were investigated from intracellularly perfused squid giant axons, C a-o(+2) and Mg-o(+2) both blocked I-K in a voltage-independent manner with a K-D of similar to 100 and 500 mM, respectively. This effect was obscured at potentials in the vicinity of the resting potential (simi lar to-60 mV) by a rightward shift of the steady-state I-K inactivatio n curve along the voltage axis. The addition of either calcium or magn esium ions to the extracellular solution also produced the well known shift of the I-K activation curve along the voltage axis, Ca-o(+2) was approximately twice as effective in this regard as Mg-o(+2). The I-K activation kinetics were slowed by Ca-o(+2), but deactivation kinetics were not altered, as shown previously. Similar results were obtained with Mg-o(+2). The addition of magnesium ions to the intracellular per fusate shifted the activation curve along the voltage axis in the nega tive direction (without producing block) by approximately the same amo ng as the Mg-o(+2) shift of this curve in the positive direction. More over, Mg-i(+2) substantially slowed the deactivation kinetics, whereas the effects of Mg-i(+2) on activation kinetics at strongly depolarize d potentials were relatively minor. At modest depolarizations, Mg-i(+2 ) significantly reduced the delay before I-K activation. These results are essentially the mirror image of the effects on gating of extracel lular divalent cations.