Origin of the potassium and voltage dependence of the cardiac inwardly rectifying K-current (IK1).
Using various voltage clamp protocols, we have examined the activation and deactivation kinetics of IK1 recorded in dissociated myocytes obtained from canine purkinje fibers. Exponential current relaxations following step changes of the membrane potential were characterized at several different K levels (5, 12, 42, and 82 mM) and several voltages (K reversal potential +/- 40 mV). We have interpreted our data according to a K-activated, K-channel model of IK1 gating. Our data suggests that at least two binding sites for extracellular K must be occupied before the channel opens and occupancy of about three more higher affinity sites for K on the open channel will slow the closing of that channel. In our model, the voltage dependency of gating arises from a combination of three voltage dependent steps: (a) isomerization between open and closed states, (b) binding of K, and (c) occupancy of the channel by internal Mg. Lowering internal K to 40 mM causes major changes in the voltage and K dependence of IK1 gating. However, these changes could be accounted for in our model by relatively small (approximately 20 to 30 mV) shifts in the voltage dependence of several of the steps that govern gating. Our data further suggest that there is an interaction between both extracellular and intracellular K levels and the ability of intracellular Mg to block the IK1 channel.
Pennefather
P
P
Faculty of Pharmacy, University of Toronto, Ontario, Canada.
Oliva
C
C
Mulrine
N
N
D000818:Animals; D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D004285:Dogs; D004563:Electrochemistry; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D008954:Models, Biological; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D011690:Purkinje Fibers / Q000378:metabolism*
D015221:Potassium Channels; D008274:Magnesium; D011188:Potassium