Calcium and voltage dependent inactivation of sodium and calcium currents limits calcium influx in helisoma neurons

Abstract

The control of free intracellular calcium concentration ([Ca2+]i) is necessary for cell survival because of the ubiquitous and essential role this second messenger plays in regulating numerous intracellular processes. Calcium regulation in neurons is especially vigorous because of the large calcium influx that occurs through voltage-gated channels during membrane depolarization. In this study we examined changes in ionic currents that can limit calcium influx into neurons during electrical activity. We found that the [Ca2+]i in electrically stimulated Helisoma B4 neurons initially increased to a peak and then relaxed to lower concentrations in tandem with a decline in the action potential peak voltage. The decline in [Ca2+]i and the peak action potential voltage in this sodium and calcium driven neuron was found to be a dual manifestation of I(Na) and I(Ca) inactivation. I(Na) and I(Ca) both displayed voltage dependent inactivation. Additionally, I(Na) and I(Ca) progressively inactivated at [Ca2+]i above 200 nM, concentrations readily attained in electrically stimulated B4 neurons. Calcium and voltage dependent I(Na) and I(Ca) inactivation were found to reduce calcium influx during continuous electrical stimulation by decreasing both the magnitude of I(Ca) that could be activated and the percent of the available I(Ca) that would be activated due to the diminished peak action potential voltage. Calculations based on data herein suggest that the voltage and calcium dependent I(Na) and I(Ca) inactivation that occurs during continuous electrical stimulation dramatically reduces calcium influx in this sodium and calcium driven neuron and thus limits the increase in [Ca2+]i.

Differential Effects of Ciguatoxin and Maitotoxin in Primary Cultures of Cortical Neurons

“…Interestingly, in cortical neurons, MTX affected VGSC decreasing peak sodium current amplitude, an effect similar to that elicited by CTX 3C. Although the mechanisms underlying the decrease in sodium current amplitude elicited by 5 nM MTX have not been addressed in this study, it is likely due to the calcium-dependent inactivation of sodium channels elicited by the calcium rise, as previously reported in other neurons …”

“…Although the mechanisms underlying the decrease in sodium current amplitude elicited by 5 nM MTX have not been addressed in this study, it is likely due to the calcium-dependent inactivation of sodium channels elicited by the calcium rise, as previously reported in other neurons. 44 We have recently shown that CTX 3C causes membrane depolarization in cortical neurons and that this effect was abolished by TTX (manuscript in preparation). Interestingly, here we observed that MTX also produces membrane depolarization in cortical neurons, which is probably related with the calcium influx elicited by the toxin.…”

Protective Effect of L-type Calcium Channel Blockers Against Haloperidol-induced Orofacial Dyskinesia: A Behavioural, Biochemical and Neurochemical Study

“…Intracellular calcium ion release and extracellular calcium ion influx is regulated by immensely complex set of signals [8][9][10][11]. Therefore, understanding the mechanism by which calcium ion regulate diverse cellular processes constitutes one of the primary goals of neuronal sciences.…”