Fig. 4. Relationship between Ca2+ entry and the release of neurotransmitter in the hippocampal medial perforant pathway. A, Time courses of [Capre]t and fEPSP in response to the manipulation of extracellular Ca2+ concentration ([Ca2+]o) in a typical experiment. At the end of each experiment, two glutamate receptor antagonists, CNQX and APV, were routinely applied to isolate the stimulation artifact and presynaptic fiber volley. This allows subtraction of the stimulation artifact and presynaptic fiber volley from the raw recording trace for a more accurate measurement of the slope of fEPSP.Inset shows sample traces taken at steady state in solutions containing 2.5 mm[Ca2+]o (control), 1.0 mm [Ca2+]o, and after application of CNQX and APV. B, Summary data of [Capre]t and fEPSP in response to each [Ca2+]o tested. The solid line is a best fit of experimental data with a Hill equation: fEPSP = fEPSPmax[([Capre]t)n/([Capre]f)n+ (Kd)n]. fEPSPmax = 150% of baseline fEPSP, andKd = 85% of baseline [Capre]t; n = 3.5.C, Comparison of the apparent power number [log(%fEPSP)/log(%[Capre]t)] as a result of selective blockade of Ca2+ channels and nonselective reduction of Ca2+ entry. The calculated apparent power numbers for ω-Aga IVA and ω-CgTx GVIA are 2.7 ± 0.5 (n = 3) and 0.4 ± 0.1 (n = 9), respectively. The calculated apparent power numbers for 4.0, 1.5, 1.0, and 0.75 mm[Ca2+]o are 0.7 ± 0.2 (n = 7), 1.7 ± 0.3 (n = 6), 2.1 ± 0.1 (n = 5), and 2.6 ± 0.3 (n = 5), respectively. This result indicates that P/Q-type channels interact with the release machinery more tightly than N-type in the hippocampal medial perforant pathway.