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Hyperpolarization makes a neuronal membrane potential more negative relative to the exterior. It is a voltage description; inhibition need not produce hyperpolarization, as shunting inhibition illustrates.

An ionotropic receptor is a receptor in which binding of a ligand directly gates an ion channel within the same protein complex. The binding site detects the chemical signal; the pore supplies a path across the cell membrane. At a chemical synapse, a neurotransmitter therefore changes synaptic conductance without an obligatory intervening G protein or second messenger. ^[ref]

A familiar example is the nicotinic acetylcholine receptor of skeletal muscle: acetylcholine binding opens a pore passing cations, including sodium and potassium. The muscarinic acetylcholine receptor instead uses intracellular signal transduction; the same neurotransmitter can engage different mechanisms. Direct gating does not mean that an ionotropic receptor pumps ions: electrochemical gradients drive passage through the open ion channel. Nor does “ionotropic” specify excitation. The reversal potential, initial membrane potential and other conductances determine whether the effect favors an action potential, causes hyperpolarization, or supplies shunting inhibition. ^[ref]

A concrete electrical approximation separates opening from drive. Let $N$ identical ion channels each have open-channel electrical conductance $\gamma$ and opening probability $p(t)$. At fixed membrane potential $V$, with common reversal potential $E_{\mathrm{rev}}$, the expected value of inward-positive electric current isFor stipulated values $N=100$, $\gamma =20\mathrm{pS}$, $p=0.2$, $V=-60\mathrm{mV}$ and $E_{\mathrm{rev}}=0$, the mean open count is $20$, the population electrical conductance is $0.4\mathrm{nS}$ and $I_{\mathrm{in}}=24\mathrm{pA}$. One open ion channel carries $1.2\mathrm{pA}$. These are illustrative values, not measurements. At $V=E_{\mathrm{rev}}$, the net electric current vanishes despite open ion channels; neither binding nor opening alone determines the readout. The approximation omits changes in ion concentrations and voltage-dependent open-channel electrical conductance.

A motivating experiment made the elementary electrical events visible. As Bert Sakmann recounts, chronically denervated frog muscle fibers had acetylcholine-sensitive receptors spread beyond the original nerve contact. Mild enzyme treatment exposed the cell membrane; a polished glass pipette sealed over a small patch to reduce background noise. Two intracellular electrodes held the local membrane potential through voltage clamp, while the patch pipette recorded tiny electric currents. Applying suberyldicholine, a ligand that activates the acetylcholine receptor and prolongs openings, revealed abrupt, approximately rectangular current events. Their amplitudes agreed reasonably with estimates from whole-membrane current fluctuations. This established discrete opening and closing events; it did not make every ligand response instantaneous. Background noise and finite recording bandwidth concealed sufficiently small or brief events.^[ref]

Recording an intact membrane patch alone does not exclude intracellular relays. Tank, Huganir, Greengard and Webb supplied a complementary isolation test in 1983: they purified nicotinic acetylcholine receptors from an electric ray's electric organ, incorporated them into artificial lipid membranes, and fused small vesicles into larger vesicles by freezing and thawing. Sealed glass-pipette recordings from isolated membrane patches resolved functional ion channels with properties resembling those in muscle. Removing the intact cytoplasm and its signaling machinery supports the sufficiency of the receptor complex for channel function; an artificial lipid environment still cannot reproduce every native regulatory interaction.^[ref]

Direct gating supports millisecond communication at many chemical synapses. Response duration also depends on neurotransmitter clearance, binding and channel-state transitions. Continued ligand exposure can prolong activity. Classify an ionotropic receptor by its direct connection between recognition and pore gating, rather than a universal duration cutoff. ^[ref]

Patch clamp connects an electrode to a small area of cell membrane through a solution-filled patch pipette. A gigaohm seal around the rim makes tiny electric currents through ion channels distinguishable from seal leak current. The beautiful change of scale is from a population's average response to individual opening and closing events in single-channel recording.

Separate two questions. The configuration determines which cell membrane is accessible: an intact patch in cell-attached recording, an excised inside-out patch or outside-out patch, or intracellular access in whole-cell recording. The recording mode determines what is commanded and what is observed: voltage clamp commands an electric potential difference and measures electric current; current clamp commands electric current and measures membrane potential. Whole-cell recording supports both modes. A patch can contain several ion channels; a small recording area does not establish that only one is present.

The 1976 article Single-channel currents recorded from membrane of denervated frog muscle fibres describes an extracellular fire-polished pipette with a $3$–$5\mu \mathrm{m}$ opening and $2$–$5\mathrm{M\Omega }$ electrical resistance. It contained saline and a channel-activating compound. Two separate intracellular electrodes supplied local voltage clamp of the muscle fibre; the patch amplifier measured local electric current. Cooling to $6$–$8{}^{\circ }\mathrm{C}$ and hyperpolarization helped resolve elementary events. Figure 2 shows step-like pulses with a $200\mathrm{Hz}$ filter at $-120\mathrm{mV}$ and $8{}^{\circ }\mathrm{C}$. Discrete amplitudes and overlapping events supported individual ion channel openings rather than a smoothly varying population response. This was neither whole-cell recording through the patch pipette nor current clamp. The specialized conditions improved visibility but limit generalization to warmer preparations; filtering can conceal brief openings.^[ref]

For a new single-channel recording experiment, useful controls include a matched recording without the activating compound, controlled membrane potential, repeated seal tests, and an explicitly stated filter frequency response. These are proposed controls, not claims that every one was performed in that 1976 figure. Changing membrane potential tests the single-channel current-voltage relation; changing the recording filter tests whether a short pulse's apparent amplitude is an instrument artifact. A flat baseline establishes neither an absence of ion channels nor an absence of very brief events.

Synaptic integration is the conversion of inputs at a neuron's synapses into a changing membrane potential and, in a spiking neuron, the timing or absence of action potentials. Spatial summation concerns inputs at different locations; temporal summation concerns inputs at different times. A useful question is whether individually ineffective inputs can act together, and whether an inhibitory postsynaptic potential changes that cooperation. The answer depends on location, timing and the receiving neuron's state.

A synaptic potential is a voltage response, whereas synaptic conductance describes activated ion channels. With inward-positive electric current, the contribution of input $j$ isHere $g_j$ is its synaptic conductance, $E_j$ its reversal potential and $V$ the local membrane potential. The driving force $E_j-V$ is an electric potential difference. An EPSP generally brings the membrane potential toward a more positive reversal potential, but its driving force shrinks during depolarization. An IPSP need not produce hyperpolarization: a reversal potential above rest but below the neuronal firing threshold can produce depolarization while opposing a larger excursion. At $E_j=V$, the added synaptic conductance initially carries zero electric current yet can cause shunting inhibition of another input.^[ref]

Two distinct nonlinearities matter. Even a passive cell membrane can show sublinear synaptic integration when added synaptic conductances reduce driving force and effective electrical resistance. Active voltage-gated ion channels and NMDA receptors can instead amplify sufficiently concentrated inputs and produce a dendritic spike. Neither summing prescribed electric currents nor adding separate measured EPSPs is an exact universal rule for a branching neuron.^[ref]