Quantitative aspects of L-type Ca2+ currents

Ca(2+) currents in neurons and muscle cells have been classified as being one of 5 types, of which four, L, N, P/Q and R were said to be high threshold and one, T, was designated low threshold. This review focuses on quantitative aspects of L-type currents. L-type channels are now distinguished according to their structure as one of four main subtypes Ca(v)1.1-Ca(v)1.4. L-type calcium currents play many fundamental roles in cellular dynamical processes including control of firing rate and pacemaking in neurons and cardiac cells, the activation of transcription factors involved in synaptic plasticity and in immune cells. The half-activation potentials of L-type currents (I(CaL)) have been ascribed values as low as -50mV and as high as near 0mV. The inactivation of I(CaL) has been found to be both voltage (VDI) and calcium-dependent (CDI) and the latter component may involve calcium-induced calcium release. CDI is often an important aspect of dynamical models of cell electrophysiology. We describe the basic components in modeling I(CaL) including activation and both voltage and calcium dependent inactivation and the two main approaches to determining the current. We review, by means of tables of values from over 65 representative studies, the various details of the dynamical properties associated with I(CaL) that have been found experimentally or employed in the last 25 years in deterministic modeling in various nervous system and cardiac cells. Distributions and statistics of several parameters related to activation and inactivation are obtained. There are few reliable complete experimental data on L-type calcium current kinetics for cells at physiological calcium ion concentrations. Neurons are divided approximately into two groups with experimental half-activation potentials that are high, ≈ -18.3mV, or low, ≈ -36.4mV, which correspond closely with those for Ca(v)1.2 and Ca(v)1.3 channels in physiological solutions. There are very few complete experimental data on time constants of activation, those available suggesting values around 0.5-2ms. In modeling, a wide range of time constants has been employed. A major problem for quantitative studies due to lack of experimental data has been the use of kinetic parameters from one cell type for others. Inactivation time constants for VDI have been found experimentally with average 65ms. Examples of calculations of I(CaL) are made for linear and constant field methods and the effects of CDI are illustrated for single and double pulse protocols and the results compared with experiment. The review ends with a discussion and analysis of experimental subtype (Ca(v)1.1-Ca(v)1.4) properties and their roles in normal, including pacemaker, activity, and many pathological states.