Glutamate metabotropic receptors increase a Ca(2+)-activated nonspecific cationic current in CA1 hippocampal neurons

Abstract

1. We studied the currents evoked in CA1 pyramidal neurons by the selective metabotropic glutamate receptor (mGluR) agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylate (1S,3R-ACPD; 100 microM, 2.30–5 min) with the single-electrode voltage-clamp technique in the continuous presence of tetrodotoxin (1 microM), bicuculline (10 microM), 6-cyano-7-nitroquinoxaline-2,3-dione (15 microM), and D-2-amino-5-phosphonovaleric acid (50 microM) to depress action potentials and synaptic activity. Microelectrodes were filled with 3M CsCl or 2 M Cs2SO4. 2. With CsCl-filled microelectrodes, bath application of 1S,3R-ACPD induced an inward current of -308 +/p 50 (SE) pA amplitude [holding potential (VH -60 mV, n = 12)] associated with a conductance decrease (26.5 +/- 5.6%, P < or = 0.0022, n = 12). The current-voltage (I–V) relation of the 1S,3R-ACPD-induced (difference) current investigated using ramp voltage commands from -130 to +10 mV had a V shape with two reversal potentials: -99.6 +/- 3.4 and -17.5 +/- 3.0 mV (n = 12). 3. In contrast, in the presence of external K+ channel blockers (2 mM Ba2+ and 6 mM Cs+ or 25 mM tetraethylammonium, 6 mM Cs+, and 3 mM 4-aminopyridine), 1S,3R-ACPD also generated an inward current, albeit of smaller amplitude (-114.2 +/- 27.5 pA, P < or = 0.003, VH -60 mV, n = 8). This current was associated with a conductance increase (20.7 +/- 3.1%, P < or = 0.0117, n = 8), decreased linearly with depolarization (from -130 to -60 mV), and reversed polarity at an estimated potential of -20.7 +/- 3.6 mV (n = 8). We refer to this current recorded in the presence of K+ channel blockers as IACPD. 4. In the presence of Cd2+ (200 microM, to block voltage-dependent Ca2+ channels that are readily activated in the presence of K+ channel blockers) and a low Ca2+ concentration (100 microM), IACPD decreased linearly from -130 to +10 mV and reversed polarity at -15.8 +/- 8.5 mV (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)