A voltage-dependent potassium current in rabbit coronary artery smooth muscle cells.
1. Voltage- and time-dependent outward currents were recorded from relaxed enzymatically isolated smooth muscle cells from the rabbit left descending coronary artery using a single pipette voltage clamp technique. The calcium-activated potassium current was blocked by inclusion of EGTA in the pipette solution and CdCl2 in the extracellular bath. 2. Outward currents were elicited with depolarizing voltage steps to potentials positive to -20 mV. Long (5 s) voltage steps revealed slow inactivation of the current with a time constant of nearly 3 s at +60 mV. Potassium was identified as the predominant charge carrier by reversal potential measurements in potassium substitution experiments. 3. The results of kinetic analyses compared favourably with the Hodgkin-Huxley model for a delayed rectifier with some deviations. The sigmoid current onset was best fitted by raising the activation variable (n) to the second power. Deactivation tail currents were consistently found to be comprised of two exponential components. The kinetics of activation and deactivation were strongly voltage-dependent from -80 to +60 mV. 4. Envelope of tails experiments showed that the scaled tail current amplitudes followed the kinetic behaviour of current activation. The contribution of each of the two exponential tail components was also measured in these experiments. They did not reveal kinetically separable currents, nor were they differentially altered by 4-aminopyridine (4-AP), tetraethylammonium (TEA), or elevated [K+]o. 5. The steady-state voltage-dependence curves for both activation and inactivation were well fitted by a Boltzmann distribution with V1/2 = -5.60 mV and k = -8.66 mV for n infinity act and V1/2 = -24.20 mV and k = 5.16 mV for n infinity act. Super-imposition of the two curves revealed a 'window' of voltage where channels are available for activation without completely inactivating. 6. Neither of the commonly used potassium channel blockers, TEA or 4-AP, were particularly effective blockers of IK, reducing current by only 50-70% at an extracellular concentration of 10 mM. TEA block was mildly voltage-dependent and was more effective in reducing current towards the end of a 500 ms depolarization. 4-AP, on the other hand, demonstrated considerable voltage-dependence and preferentially reduced early currents. 7. Outward currents recorded from guinea-pig and human coronary artery myocytes under the same conditions as in the rabbit cell experiments displayed similar characteristics.(ABSTRACT TRUNCATED AT 400 WORDS)
Volk
K A
KA
Department of Physiology and Biophysics, University of Iowa, College of Medicine, Iowa City 52242.
Matsuda
J J
JJ
Shibata
E F
EF
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D003331:Coronary Vessels; D004533:Egtazic Acid / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D004533:Egtazic Acid; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D002118:Calcium