{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T08:33:48Z","timestamp":1768466028906,"version":"3.49.0"},"reference-count":0,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[1993,4,1]],"date-time":"1993-04-01T00:00:00Z","timestamp":733622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[1993,4]]},"abstract":"<jats:p>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\u2010cell mode using the nystatin \u2018perforated\u2019\u2010patch technique, by which the muscarinic ACh response can be continuously recorded without so\u2010called \u2018run\u2010down\u2019 phenomenon. The amount of intracellular free Ca2+ ([Ca2+]i) was fluorometrically measured using fura\u20102. 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 \u201040 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\u2010induced 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\u2010induced transient outward current increased in a sigmoidal fashion with increase in ACh concentration, where the half\u2010maximal concentration (EC50) and the Hill coefficient (n) were 8 x 10(\u20107) M and 1.9, respectively. Both muscarine and carbamylcholine mimicked the ACh response, but neither McN\u2010A\u2010343 (M1 agonist) nor oxotremorine (cardiac M2 agonist) induced any current. 6. Muscarinic antagonists reversibly blocked the ACh response in a concentration\u2010dependent manner. The inhibitory potency was in the order of atropine &gt; pirenzepine &gt; AF\u2010DX\u2010116. 7. The ACh\u2010induced transient outward current was never recorded when [Ca2+]i was chelated by the acetoxymethyl ester form of 1,2\u2010bis(O\u2010aminophenoxy)ethane\u2010N,N,N',N'\u2010tetraacetic acid (BAPTA AM). On the other hand, in Ca(2+)\u2010free 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\u20102 imaging showed that [Ca2+]i was increased when ACh was added to the external medium with or without Ca2+, though in Ca(2+)\u2010free 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\u2010threshold 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\u20107, chlorpromazine and trifluoperazine reversibly inhibited the ACh response in a concentration\u2010dependent manner.(ABSTRACT TRUNCATED AT 400 WORDS)<\/jats:p>","DOI":"10.1113\/jphysiol.1993.sp019612","type":"journal-article","created":{"date-parts":[[2014,12,17]],"date-time":"2014-12-17T14:37:07Z","timestamp":1418827027000},"page":"585-604","source":"Crossref","is-referenced-by-count":71,"title":["Hyperpolarizing muscarinic responses of freshly dissociated rat hippocampal CA1 neurones."],"prefix":"10.1113","volume":"463","author":[{"given":"M","family":"Wakamori","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Hidaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Akaike","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[1993,4]]},"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.1993.sp019612","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.1993.sp019612","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T03:16:48Z","timestamp":1698203808000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.1993.sp019612"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,4]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1993,4]]}},"alternative-id":["10.1113\/jphysiol.1993.sp019612"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.1993.sp019612","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,4]]}}}