The Effectiveness of Various Blockers of L-Type Voltage -gated Ca2+ Channels in Suppression of KC1-induced Calcium Responses in Hippocampal Neurons

Voltage-gated L-type calcium channels are expressed by various types of mammalian cells. These channels are usually located postsynaptically in neurons and are responsible for transmitting the excitatory signal and activation of Ca2+-dependent signaling cascades. One of the main approaches for studying the functions of voltage-gated channels is the use of various synthetic blockers. This work aimed to compare four blockers from three_pharmacological groups and determine the concentration required to completely suppress the influx of Ca2+ through L-type channels in cultured hippocampal neurons in response to depolarization induced by the application of KCI. We show that although an increase in intracellular Ca2+ concentration in response to depolarization is primarily mediated by the entry of Ca2+ through L-type channels, the activation of other voltage-dependent calcium channels also significantly contributes to Ca2+ influx in this case. In this regard, nifedipine and isradipine, which, apparently, are more selective in relation to L-channels, approximately halve the amplitude of the calcium response. In turn, diltiazem and verapamil completely blocked KCI-induced Ca2+ influx due to non-specific blocking of other non-L-type calcium channels. It should be noted that the concentration of blockers required for the complete suppression of Ca2+ influx through voltage-gated channels was 300 mu M in both cases, while the IC50 in the case of diltiazem and verapamil was 54.2 mu M and 56.4 mu M, respectively. Thus, substances from the dihydropyridine group are preferable to use if substantial selectivity to L-type channels is required. In turn, high concentrations of verapamil and diltiazem can be used if it is necessary to block most of the voltage-dependent calcium channels.

Automated summary

The study compared the effects of four blockers on suppressing Ca2+ influx through L-type calcium channels in cultured hippocampal neurons induced by KCl. Dihydropyridine substances were found to be more selective while verapamil and diltiazem could completely block most of the voltage-dependent calcium channels.