Differential Distribution of Three Members of a Gene Family Encoding Low Voltage-Activated (T-Type) Calcium Channels

TLDR

T-type calcium currents are present in many central and peripheral neurons and exhibit distinct physiological and functional properties. The study used in situ hybridization to map the expression of the three T-type calcium channel transcripts α1G, α1H, and α1I in the central and peripheral nervous system. The transcripts showed distinct, largely complementary distributions, with high expression in specific neuronal populations (e.g., α1G in inferior olivary and thalamic relay neurons, α1H in sensory ganglia and dentate gyrus, α1I in thalamic reticular neurons), some neurons co‑expressing all three, and overall patterns supporting the hypothesis that differential gene expression underlies the pharmacological and physiological heterogeneity of T‑type calcium currents.

Abstract

Low voltage-activated (T-type) calcium currents are observed in many central and peripheral neurons and display distinct physiological and functional properties. Using in situ hybridization, we have localized central and peripheral nervous system expression of three transcripts (α1G, α1H, and α1I) of the T-type calcium channel family (Ca V T). Each mRNA demonstrated a unique distribution, and expression of the three genes was largely complementary. We found high levels of expression of these transcripts in regions associated with prominent T-type currents, including inferior olivary and thalamic relay neurons (which expressed α1G), sensory ganglia, pituitary, and dentate gyrus granule neurons (α1H), and thalamic reticular neurons (α1I and α1H). Other regions of high expression included the Purkinje cell layer of the cerebellum, the bed nucleus of the stria terminalis, the claustrum (α1G), the olfactory tubercles (α1H and α1I), and the subthalamic nucleus (α1I and α1G). Some neurons expressed high levels of all three genes, including hippocampal pyramidal neurons and olfactory granule cells. Many brain regions showed a predominance of labeling for α1G, including the amygdala, cerebral cortex, rostral hypothalamus, brainstem, and spinal cord. Exceptions included the basal ganglia, which showed more prominent labeling for α1H and α1I, and the olfactory bulb, the hippocampus, and the caudal hypothalamus, which showed more even levels of all three transcripts. Our results are consistent with the hypothesis that differential gene expression underlies pharmacological and physiological heterogeneity observed in neuronal T-type calcium currents, and they provide a molecular basis for the study of T-type channels in particular neurons.