Purinergic Signalling (2006) 2:545–557 DOI 10.1007/s11302-006-9004-4 ORIGINAL ARTICLE Excitatory effect of ATP on rat area postrema neurons Masaru Sorimachia & Minoru Wakamoria & Norio Akaikeb Received: 11 October 2005 / Accepted: 26 January 2006 / Published online: 30 May 2006 # Springer Science + Business Media B.V. 2006 Abstract ATP-induced inward currents and increases in the cytosolic Ca2+ concentration ([Ca]in) were investigated in neurons acutely dissociated from rat area postrema using whole-cell patch-clamp recordings and fura-2 microﬂuorometry, respectively. The ATP- induced current (IATP) and [Ca]in increases were mimicked by 2-methylthio-ATP and ATP-gS, and were inhibited by P2X receptor (P2XR) antagonists. The current–voltage relationship of the IATP exhibited a strong inward rectiﬁcation, and the amplitude of the IATP was concentration-dependent. The IATP was markedly reduced in the absence of external Na+, and the addition of Ca2+ to Na+-free saline increased the IATP. ATP did not increase [Ca]in in the absence of external Ca2+, and Ca2+ channel antagonists partially inhibited the ATP-induced [Ca]in increase, indicating that ATP increases [Ca]in by Ca2+ inﬂux through both P2XR channels and voltage-dependent Ca2+ channels. There was a negative interaction between P2XR- and nicotinic ACh receptor (nAChR)-channels, which depended on the amplitude and direction of current ﬂow through either channel. Current occlusion was M. Sorimachia (*) : M. Wakamoria : N. Akaikeb Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 890-8520, Japan e-mail: ciliary@m.kufm.kagoshima-u.ac.jp Research Division for Life Sciences, Kumamoto Health Science University, Kumamoto, 861-5598, Japan observed at Vhs between j70 and j10 mV when the IATP and ACh-induced current (IACh) were inward, but no occlusion was observed when these currents were outward at a Vh of +40 mV. The IATP was not inhibited by co-application of ACh when the IACh was markedly decreased either by removal of permeant cations, by setting Vh close to the equilibrium potential of IACh, or by the addition of d-tubocurarine or serotonin. These results suggest that the inhibitory interaction is attributable to inward current ﬂow of cations through the activated P2XR- and nAChR- channels. Keywords ATP . ACh . cytosolic Ca2+ concentration . Fura-2 microﬂuorometry . negative interaction between nicotinic and P2X channels . whole-cell patch-clamp recording Introduction The rat area postrema (AP) is a medullary circum- ventricular organ located in the hindbrain at the level of the obex, with a dense vascular supply devoid of a blood–brain barrier. The lack of a blood–brain barrier makes the AP ideally placed to act as a chemosensitive trigger zone involved in the control of vomiting in response to circulating emetic substances (Borison [1, 2]). Neurons in the AP are also responsive to changes in osmolarity or sodium concentration (Franchini et al. [3]), and can be activated by circulating vasoactive peptides such as angiotensin II (Fink et al. [4]), and arg-vasopressin (Undesser et al.