Table 1.

Key Differences Between 4AP and 0 Mg²⁺ Models.^a

		4-Aminopyridine	0 Magnesium
Primary pharmacology		Blocks voltage-gated K+ channels	Relieves voltage-dependent NMDA s blockade: enhances Glut neurotransmission
Secondary pharmacology		Effects more apparent in interneurons	Reduces divalent cation shielding—shift in voltage-dependence, enhancing excitability
Primary effect on cell activity		IN burst firing enhanced	Enhances synaptic summation in dendrites
Early interictal activity patterns		Primary IN activity	Glutamatergic, with secondary IN activity
Brain area patterns	Early	Prominent Hipp activity; also NC & EC	NC/EC IIDs; Minimal Hipp involvement
	Intermediate	SLEs in NC, referred to Hipp	SLEs in NC/EC; Minimal Hipp involvement
	Late	Late recurrent discharges; Hipp led, spreading to NC/EC	Late recurrent discharges; Hipp led, spreading to NC/EC
Seizure induction by optogenetic IN activation		Yes	Only in late stage
Electrographic SLE pattern		Low-voltage, fast activity	Hypersynchronous-onset

Abbreviations: 4AP, 4-aminopyridine; EC, entorhinal cortex; Hipp, Hippocampus; IIDs, interictal discharges; IN, interneurons; NC, neocortex; SLEs, seizure-like events.

^a See Codadu et al ^20,21 for details; also Levesque et al ²² and de Curtis and Avoli ²³ about the electrographic SLE patterns at seizure onset, and Chang et al ²⁴ regarding SLEs being triggered in 0 Mg²⁺ by optogenetic interneuronal activation only once seizure-like activity is well established, and not early in that model.