Developmental changes in voltage-activated potassium currents of rat retinal ganglion cells.
Ca2(+)-independent voltage-activated potassium currents were investigated during the differentiation of rat retinal ganglion cells. Whole-cell patch-clamp recordings of Ca2(+)-independent voltage-activated potassium currents and their individual current components, i.e. a sustained, tetraethylammonium-sensitive current, a transient, 4-aminopyridine-sensitive current, and a slowly decaying current that was blocked by Ba2+, revealed distinct ontogenetic modifications in current densities and in activation and inactivation parameters. All three current types were expressed simultaneously at embryonic day 17/18 and were present in all retinal ganglion cells thereafter without showing any significant changes until the end of the first postnatal week. Ca2(+)-independent voltage-activated potassium current densities then increased strongly from postnatal day 8 onwards. Tetraethylammonium-sensitive current density increased about eightfold from 74 pA/pF in embryonic stages to 586 pA/pF in adult cells, whereas the transient potassium currents blocked by 4-aminopyridine increased only about 2.5-fold from 174 pA/pF to 442 pA/pF. The Ba2(+)-sensitive current increased simultaneously from 35 pA/pF to 332 pA/pF. The much higher increase in the sustained current components during retinal ganglion cell differentiation accounted for the changes in decay kinetics of Ca2(+)-independent voltage-activated potassium current observed in later postnatal stages. Alterations in current densities were paralleled by pronounced changes in current kinetics. From postnatal day 8 onwards, activation of Ca2(+)-independent voltage-activated potassium current was right-shifted for about 10 mV owing to a shift in tetraethylammonium-sensitive current-activation, whereas activation of other K+ components remained unaltered. Tetraethylammonium-sensitive current steady-state inactivation was incomplete at all developmental stages. About 50% of the tetraethylammonium-sensitive current elicited by a depolarization to +36 mV did not inactivate after prepulse potentials positive to -10 mV. In contrast, transient potassium current blocked by 4-aminopyridine almost fully inactivated during embryonic stages, whereas in adult retinal ganglion cells about 40% of this current component did not inactivate after prepulse potentials positive to -20 mV. Parallel investigation of the resting membrane potential during retinal ganglion cells differentiation showed an exponential increase from -3 mV at embryonic day 15/16 when no voltage-activated ion currents were expressed to a final value of -58 mV at postnatal day 8. These results show that fundamental potassium current modifications occur relatively late in retinal ganglion cell development and only after the resting potential is at its final value.
Reiff
D F
DF
Department of Pathophysiology of Vision and Neuro-Ophthalmology, University Eye Hospital, Tübingen, Germany.
Guenther
E
E
D015761:4-Aminopyridine / Q000494:pharmacology; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D004553:Electric Conductivity; D004594:Electrophysiology; D004622:Embryo, Mammalian / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D011188:Potassium / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D012165:Retinal Ganglion Cells / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology
D019789:Tetraethylammonium; D015761:4-Aminopyridine; D011188:Potassium; D002118:Calcium