Tetrahydroaminoacridine (THA) reduces voltage-dependent calcium currents in rat sensory neurons. 1991

K M Kelly, and R A Gross, and R L Macdonald
Department of Neurology, University of Michigan Medical Center, Ann Arbor 48109.

Tetrahydroaminoacridine (THA) is a centrally active anticholinesterase that also interacts with neuronal K+ and Na+ channels and cardiac Ca2+ channels. The effects of THA on neuronal voltage-dependent Ca2+ channels are not known. We tested the effects of THA (25 nM-250 microM) on the Ca2+ current components of acutely dissociated rat nodose ganglion and dorsal root ganglion (DRG) neurons using the whole cell patch clamp recording technique. THA reduced the low-threshold (T) and high-threshold (N/L) Ca2+ current components in a concentration-dependent manner (IC50 approximately equal to 125 microM for T; approximately equal to 80 microM for N/L). Minimal current reduction was seen below approximately 10 microM. Our results show that THA reduces voltage-dependent Ca2+ currents in rodent sensory neurons suggesting another means by which THA may affect Ca(2+)-dependent physiologic processes.

UI MeSH Term Description Entries
D009475 Neurons, Afferent Neurons which conduct NERVE IMPULSES to the CENTRAL NERVOUS SYSTEM. Afferent Neurons,Afferent Neuron,Neuron, Afferent
D009620 Nodose Ganglion The inferior (caudal) ganglion of the vagus (10th cranial) nerve. The unipolar nodose ganglion cells are sensory cells with central projections to the medulla and peripheral processes traveling in various branches of the vagus nerve. Nodose Ganglia,Ganglia, Nodose,Ganglion, Nodose
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002800 Cholinesterase Inhibitors Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. Acetylcholinesterase Inhibitor,Acetylcholinesterase Inhibitors,Anti-Cholinesterase,Anticholinesterase,Anticholinesterase Agent,Anticholinesterase Agents,Anticholinesterase Drug,Cholinesterase Inhibitor,Anti-Cholinesterases,Anticholinesterase Drugs,Anticholinesterases,Cholinesterase Inhibitors, Irreversible,Cholinesterase Inhibitors, Reversible,Agent, Anticholinesterase,Agents, Anticholinesterase,Anti Cholinesterase,Anti Cholinesterases,Drug, Anticholinesterase,Drugs, Anticholinesterase,Inhibitor, Acetylcholinesterase,Inhibitor, Cholinesterase,Inhibitors, Acetylcholinesterase,Inhibitors, Cholinesterase,Inhibitors, Irreversible Cholinesterase,Inhibitors, Reversible Cholinesterase,Irreversible Cholinesterase Inhibitors,Reversible Cholinesterase Inhibitors
D004056 Differential Threshold The smallest difference which can be discriminated between two stimuli or one which is barely above the threshold. Difference Limen,Just-Noticeable Difference,Weber-Fechner Law,Difference Limens,Difference, Just-Noticeable,Differences, Just-Noticeable,Differential Thresholds,Just Noticeable Difference,Just-Noticeable Differences,Law, Weber-Fechner,Limen, Difference,Limens, Difference,Threshold, Differential,Thresholds, Differential,Weber Fechner Law
D004594 Electrophysiology The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D005727 Ganglia, Spinal Sensory ganglia located on the dorsal spinal roots within the vertebral column. The spinal ganglion cells are pseudounipolar. The single primary branch bifurcates sending a peripheral process to carry sensory information from the periphery and a central branch which relays that information to the spinal cord or brain. Dorsal Root Ganglia,Spinal Ganglia,Dorsal Root Ganglion,Ganglion, Spinal,Ganglia, Dorsal Root,Ganglion, Dorsal Root,Spinal Ganglion
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013619 Tacrine A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders. Tetrahydroaminoacridine,1,2,3,4-Tetrahydro-9-acridinamine,1,2,3,4-Tetrahydroaminoacridine,9-Amino-1,2,3,4-Tetrahydroacridine,Cognex,Romotal,THA,Tacrine Hydrochloride,Tenakrin
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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