ABSTRACT
On isolated retinal preparation from STZ-induced diabetic rats in whole-cell configuration the basic electrical properties of retinal ganglion cells (RGC) were studied. It was shown that on 8th week after STZ maximal depolarization-induced firing frequency is reduced and decay time constant of high-frequency stimulation-induced calcium signals is increased as compared to controls. The data obtained suggest functional changes in RGC of STZ-induced diabetic rats, possible mechanisms of such changes are discussed.
Subject(s)
Diabetes Mellitus, Experimental/physiopathology , Membrane Potentials/physiology , Retinal Ganglion Cells/physiology , Streptozocin/pharmacology , Animals , Calcium Signaling/physiology , Cell Membrane/drug effects , Cell Membrane/metabolism , Cell Membrane/physiology , Diabetes Mellitus, Experimental/metabolism , Electric Stimulation , In Vitro Techniques , Membrane Potentials/drug effects , Patch-Clamp Techniques , Rats , Retinal Ganglion Cells/drug effectsABSTRACT
High frequency firing properties of the rat retinal ganglion cells and role of 4-AP-sensitive potassium current in firing generation were studied using whole cell patch-clamp techniques. Potassium channel blocker 4-AP (0,2 mM) reduced depolarization-evoked firing rate by 62% (from 50 +/- 5, n = 12 to 19 +/- 2 Hz, n = 7). Single action potential parameters were affected: half-width was increased by 133% (from 1,2 +/- 0,1, n = 12 to 2,8 +/- 0,3 ms, n = 7), decay slope was decreased by 63% (from 102 +/- 11, n = 12 to 38 +/- 7 mV/ms, n = 7) and afterhyperpolarization amplitude by 83% (from 18 +/- 2, n = 12 to 3 +/- 2 mV, n = 7). 4-AP application (0,2 mM) reduced potassium current amplitude of the retinal neurons. 4-AP-sensitive current was obtained by digital subtraction of current that was registered in the presence of the blocker from control current records (1,61 +/- 0,22 nA, n = 6). 4-AP-sensitive current was equal to 0,40 +/- 0,09 nA (n = 6). Thus, moderate (25%) reducing of potassium current amplitude leads to essential changes in firing properties of retinal neurons. 4-AP-sensitive residual current was similar to Kv3.1/Kv3.2 potassium currents that were described in literature previously. Moreover, we excluded the possibility of 4-AP influence on Kv1 channels by specific blocker alpha-dendrotoxin (100 nM) application. Such applications significantly affected neither firing frequency nor single action potential parameters. The data obtained suggest that 4-AP-sensitive current plays a key role in high frequency firing generation in the rat retinal ganglion cells. We assume that the 4-AP-sensitive current is mediated by Kv3.1/Kv3.2 conductance.
