Electrophysiological Analysis of the Functional State of Spinal Cord Motoneurons in Rats with Parathyroprivous Tetany

Abstract

Calcium ions are known to have a direct involvement in controlling and regulating a wide spectrum of neuron functions, including the growth of processes, synaptogenesis, synaptic transmission, plasticity, and survival, and dysregulation of these functions leads to the development of synaptic dysfunction, impaired plasticity, and the development of various neuropathological disorders [15,22]. The discovery of the ability of calcium to work as an external ligand allowed it to be regarded as a fi rst messenger [11]. Infl ux of Ca 2+ through voltage-and ligand-dependent channels in the plasma membrane makes it the main trigger for transmitter release from presynaptic terminals [10,32]. This transmitter release is under the control of N and P/Q Ca 2+ channels, such that decreases in Ca 2+ levels lead to impairment to transmitter release and, thus, normal neuron functioning [24]. Further studies showed that neuron activity is accompanied by increases in transiently calmodulin-bound cytosolic Ca 2+ concentrations as a second messenger, though in aging and disease the ability of neurons to control Ca 2+ levels is impaired [22]. Decreases in calcium ions in the surrounding medium are accompanied by impairments to the membrane permeability of the Na + / Ca 2+ exchange mechanism, with effl ux of Ca 2+ from and infl ux of Na + into the cytoplasm, leading ultimately to depolarization of cell membranes and increases in cell excitability [1]. Studies using the hippocampus as an example showed that low Ca 2+ levels combined with high K + act together to generate stable epileptiform activity [14]. These authors also demonstrated that in conditions of blockade of synaptic transmission, epileptiform activity can be induced by a non-synaptic mechanism [14]. It should be emphasized that all these calcium-dependent processes are under the specifi c control of the calcium-regulating system, where the key role is played by parathyroid hormone (PTH), produced by the parathyroid glands. PTH, as we have demonstrated [2,21], is a major modulator of the functional activity of neurons which operate as the target for hormone action. This action of PTH A comparative analysis of baseline activity, tetanic and post-tetanic increases and decreases in the frequencies of spinal cord motoneuron responses to high-frequency (50 and 100 Hz) stimulation (HFrS) of the fl exor (G) and extensor (P) nerves of the hindlimb was performed in normal rats and rats with parathyroprivous (hypocalcemic) tetany. Experiments were run using on-line selection and programmed analysis of spike activity. Signifi cant shifts in tetanic and post-tetanic motoneuron activity were recorded on days 3-7 and 21-22 of the development of acute and chronic tetanization respectively, without any signifi cant change in baseline activity. Along with sharp increases in post-stimulus excitatory changes in activity in response to HFrS during the development of acute tetany, there was relative weakening in animals with chronic tetany. At the same time, there was weakening or complete disapp...