HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wakamori, M Articles by Akaike, N Search for Related Content PubMed PubMed Citation Articles by Wakamori, M Articles by Akaike, N

Department of Neurophysiology, Tohoku University School of Medicine, Sendai, Japan.

1. Intracellular mechanisms of the muscarinic acetylcholine (ACh) response were investigated in pyramidal neurones freshly dissociated from the rat hippocampal CA1 region. Current recordings were made in the whole-cell mode using the nystatin 'perforated'-patch technique, by which the muscarinic ACh response can be continuously recorded without so-called 'run-down' phenomenon. The amount of intracellular free Ca2+ ([Ca2+]i) was fluorometrically measured using fura-2. 2. In current clamp conditions, ACh induced a transient hyperpolarization accompanied by a decrease in membrane input resistance. 3. Under voltage clamp conditions at a holding potential (Vh) of -40 mV, ACh induced two types of muscarinic currents observed either alone or together: a transient outward current and a slowly activating sustained inward current. 4. The ACh-induced transient outward current reversed the direction at K+ equilibrium potential (EK), and the reversal potential (EACh) shifted 56.7 mV for a tenfold change of extracellular K+ concentration ([K+]o). 5. The ACh-induced transient outward current increased in a sigmoidal fashion with increase in ACh concentration, where the half-maximal concentration (EC50) and the Hill coefficient (n) were 8 x 10(-7) M and 1.9, respectively. Both muscarine and carbamylcholine mimicked the ACh response, but neither McN-A-343 (M1 agonist) nor oxotremorine (cardiac M2 agonist) induced any current. 6. Muscarinic antagonists reversibly blocked the ACh response in a concentration-dependent manner. The inhibitory potency was in the order of atropine > pirenzepine > AF-DX-116. 7. The ACh-induced transient outward current was never recorded when [Ca2+]i was chelated by the acetoxymethyl ester form of 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA AM). On the other hand, in Ca(2+)-free external solution containing 2 mM EGTA and 10 mM Mg2+, the ACh response was elicited by the first application and successive ACh applications did not induce any response. Fura-2 imaging showed that [Ca2+]i was increased when ACh was added to the external medium with or without Ca2+, though in Ca(2+)-free medium only the first application of ACh increased the [Ca2+]i. 8. The ACh response was not affected by pretreatment with pertussis toxin (PTX) but the inhibitory effect of ACh on the high-threshold Ca2+ channel was abolished completely. 9. Pretreatment with Li+ enhanced the amplitude of the transient outward current and the increase in [Ca2+]i induced by ACh. 10. The calmodulin antagonists W-7, chlorpromazine and trifluoperazine reversibly inhibited the ACh response in a concentration-dependent manner.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				J.-W. Sohn, D. Lee, H. Cho, W. Lim, H.-S. Shin, S.-H. Lee, and W.-K. Ho Receptor-specific inhibition of GABAB-activated K+ currents by muscarinic and metabotropic glutamate receptors in immature rat hippocampus J. Physiol., April 15, 2007; 580(2): 411 - 422. [Abstract] [Full Text] [PDF]

				L. Zhao, Y.-P. Kuo, A. A. George, J.-H. Peng, M. S. Purandare, K. M. Schroeder, R. J. Lukas, and J. Wu Functional Properties of Homomeric, Human {alpha}7-Nicotinic Acetylcholine Receptors Heterologously Expressed in the SH-EP1 Human Epithelial Cell Line J. Pharmacol. Exp. Ther., June 1, 2003; 305(3): 1132 - 1141. [Abstract] [Full Text] [PDF]

				K. Matsushita, M. Wakamori, I. J. Rhyu, T. Arii, S.-i. Oda, Y. Mori, and K. Imoto Bidirectional Alterations in Cerebellar Synaptic Transmission of tottering and rolling Ca2+ Channel Mutant Mice J. Neurosci., June 1, 2002; 22(11): 4388 - 4398. [Abstract] [Full Text] [PDF]

				S. Katsurabayashi, H. Kubota, Z. M. Wang, J. S. Rhee, and N. Akaike cAMP-Dependent Presynaptic Regulation of Spontaneous Glycinergic IPSCs in Mechanically Dissociated Rat Spinal Cord Neurons J Neurophysiol, January 1, 2001; 85(1): 332 - 340. [Abstract] [Full Text] [PDF]

				C. D. Fiorillo and J. T. Williams Cholinergic Inhibition of Ventral Midbrain Dopamine Neurons J. Neurosci., October 15, 2000; 20(20): 7855 - 7860. [Abstract] [Full Text] [PDF]

				Y. Mori, M. Wakamori, S.-i. Oda, C. F. Fletcher, N. Sekiguchi, E. Mori, N. G. Copeland, N. A. Jenkins, K. Matsushita, Z. Matsuyama, et al. Reduced Voltage Sensitivity of Activation of P/Q-Type Ca2+ Channels is Associated with the Ataxic Mouse Mutation Rolling Nagoya (tgrol) J. Neurosci., August 1, 2000; 20(15): 5654 - 5662. [Abstract] [Full Text] [PDF]

				M. Wakamori, K. Yamazaki, H. Matsunodaira, T. Teramoto, I. Tanaka, T. Niidome, K. Sawada, Y. Nishizawa, N. Sekiguchi, E. Mori, et al. Single Tottering Mutations Responsible for the Neuropathic Phenotype of the P-type Calcium Channel J. Biol. Chem., December 25, 1998; 273(52): 34857 - 34867. [Abstract] [Full Text] [PDF]

				D. L. Sodickson and B. P. Bean Neurotransmitter Activation of Inwardly Rectifying Potassium Current in Dissociated Hippocampal CA3 Neurons: Interactions among Multiple Receptors J. Neurosci., October 15, 1998; 18(20): 8153 - 8162. [Abstract] [Full Text] [PDF]