The Intracellular Ca2+ Concentration at the Terminal Region of Retinal Bipolar Cells

Abstract

Abstract: : Purpose: The bipolar cell of the vertebrate retina gives rise to graded responses to light stimuli and transmits the responses to the inner retinal circuit. The transmitter release from presynaptic terminal is known to be directly related to the intracellular calcium concentration in the axon terminal region ([Ca²⁺]_i). Computer simulations using a biophysical model were carried to elucidate [Ca²⁺]_i change during light-induced responses. Methods: The software NEURON was used for simulations. The model cell morphology was constructed from on-type cone bipolar cell of the mouse retina. L-type and T-type voltage-gated Ca²⁺ conductances (VDCCs) were incorporated as the Ca²⁺-influx machinery. The plasma membrane Ca ATPase, the Na⁺/Ca²⁺ exchanger, the intracellular fixed buffer and diffusion were incorporated as the Ca²⁺-regulation machinery and were distributed uniformly over the entire cell. Kinetics of these machineries was estimated from previous studies. The model cell was voltage clamped either -20 mV or -70 mV from a holding potential of –45 mV. Results: In a model cell in which L-type and T-type VDCCs were distributed uniformly over the entire cell, [Ca²⁺]_i increased to 1-2 µM from 0.5 µM in response to a +25 mV 500 ms depolarizing pulse. [Ca²⁺]_i increased to about 6 µM from 2.3 µM in response to the same depolarization, when two types of VDCCs were locally distributed at the terminal region with keeping the mount of whole cell Ca²⁺-current constant. In the locally distributed model cell, [Ca²⁺]_i decreased to about 70 nM from 2.3 µM when the -25 mV 500 ms hyperpolarizing pulse was applied. Moreover, a transient [Ca²⁺]_i elevation to 11 µM was induced in response to the depolarization to the holding potential of -45 mV. Conclusions: The localization of VDCCs boosts up the range of [Ca²⁺]_i change at the terminal region to facilitate the transmitter release. In such cells, prominent transient [Ca²⁺]_i responses were induced by T-type VDCC. Therefore the signal transmission in mammalian bipolar cells might possess highly transient characteristics.

Keywords: bipolar cells • calcium • computational modeling