Journal
JOURNAL OF GENERAL PHYSIOLOGY
Volume 153, Issue 2, Pages -Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1085/jgp.202012687
Keywords
-
Categories
Funding
- National Institutes of Health [R01-EY14047, R01-NS114210]
- National Eye Institute core grant [P30-EY012576]
Ask authors/readers for more resources
The study reveals that K(v)2.1 channels carry 70-80% of the non-NKX outward dark current in mouse rods, and their loss results in increased Ca2+ influx and intracellular Ca2+ levels, leading to progressive degeneration.
Vertebrate retinal photoreceptors signal light by suppressing a circulating dark current that maintains their relative depolarization in the dark. This dark current is composed of an inward current through CNG channels and NCKX transporters in the outer segment that is balanced by outward current exiting principally from the inner segment. It has been hypothesized that K(v)2.1 channels carry a predominant fraction of the outward current in rods. We examined this hypothesis by comparing whole cell, suction electrode, and electroretinographic recordings from K(v)2.1 knockout (K(v)2.1(-/-)) and wild-type (WT) mouse rods. Single cell recordings revealed flash responses with unusual kinetics, and reduced dark currents that were quantitatively consistent with the measured depolarization of the membrane resting potential in the dark. A two compartment (outer and inner segment) physiological model based on known ionic mechanisms revealed that the abnormal K(v)2.1(-/-) rod photoresponses arise principally from the voltage dependencies of the known conductances and the NCKX exchanger, and a highly elevated fraction of inward current carried by Ca2+ through CNG channels due to the aberrant depolarization. K(v)2.1(-/-) rods had shorter outer segments than WT and dysmorphic mitochondria in their inner segments. Optical coherence tomography of knockout animals demonstrated a slow photoreceptor degeneration over a period of 6 mo. Overall, these findings reveal that K(v)2.1 channels carry 70-80% of the non-NKX outward dark current of the mouse rod, and that the depolarization caused by the loss of K(v)2.1 results in elevated Ca2+ influx through CNG channels and elevated free intracellular Ca2+, leading to progressive degeneration.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available