GABA Transporter Reversal Potential

Transport of γ-aminobutyric acid (GABA) into neurons and glia is accomplished by plasma membrane Na⁺- and Cl^--coupled GABA transporters (Nelson, 1998; Chen et al., 2004). The GABA transporters are electrogenic and, thus, their activity can be studied by using electrophysiological methods (Kavanaugh et al., 1992; Mager et al., 1993, 1996; Biedermann et al., 2002). The ion-substrate stoichiometry has been determined to be 2 Na⁺ : 1 Cl^- : 1 GABA (Pastuszko et al., 1982; Radian and Kanner, 1983; Loo et al., 2000). Thus, during a typical transport cycle, 2 Na⁺ ions, 1 Cl^- ion, 1 GABA molecule are co-translocated across the plasma membrane. Physiologically, transport is driven primarily by the Na⁺ electrochemical gradient. Cl^- is also a transported co-substrate and there is some evidence in favor of a thermodynamic role of Cl^- in the transport cycle (Keynan and Kanner, 1988; Lu and Hilgemann, 1999). As the transporter is electrogenic, it is readily seen that transport is also influenced by the membrane potential. Depending on Na⁺, Cl^-, and GABA gradients and the membrane potential, transport may be in the forward direction, in the reverse direction, or at equilibrium (i.e., no net transport) (Gaspary et al., 1998; Lu and Hilgemann, 1999; Wu et al., 2001, 2003; Wang et al., 2003). The known stoichiometry of the transport cycle can be used to determine the membrane potential at which the transporter would be at equilibrium (Lu and Hilgemann, 1999; Richerson and Wu, 2003). As the role of Cl^- is not yet fully understood (Loo et al., 2000; Sacher et al., 2002; Giovannardi et al., 2003; Karakossian et al., 2005), the equation used here should be thought of as a working model whose predictions must be tested against experimental results. Support for the validity of this equation comes from the work of Lu and Hilgemann (1999) and Wu et al. (2007).

• V_rev is the reversal potential. This is the membrane potential at which no net transport is mediated by the GABA transporter. If the membrane potential is more negative than V_rev, forward Na⁺/Cl^-/GABA cotransport takes place (i.e., Na⁺, Cl^-, and GABA are cotransported across the plasma membrane from the extracellular fluid and released into the cytoplasmic compartment). If, on the other hand, the membrane potential is more positive than V_rev, outward or reverse transport takes place (i.e., Na⁺, Cl^-, and GABA are transported out of the cycoplasm and released into the extracellular fluid). Therefore, it is easily seen that the concentration gradients of Na⁺, Cl^-, and GABA, as well as the membrane potential can determine the direction of transport. Note that the unit of V_rev is the Volt. However, the reversal potential is typically reported in millivolts (mV).
• R is the universal gas constant (8.314 J.K^-1.mol^-1).
• T is the temperature in Kelvin (°K = °C + 273.15).
• z_Na is the valence of Na⁺ (+1).
• z_Cl is the valence of Cl^- (-1).
• F is the Faraday's constant (96485 C.mol^-1).
• [GABA]_o is the concentration of GABA in the extracellular fluid. Note that the extracellular and intracellular concentration units must match.
• [GABA]_i is the concentration of GABA in the intracellular fluid. Note that the extracellular and intracellular concentration units must match.
• [Na]_o is the concentration of Na⁺ in the extracellular fluid. Note that the extracellular and intracellular concentration units must match.
• [Na]_i is the concentration of Na⁺ in the intracellular fluid. Note that the extracellular and intracellular concentration units must match.
• [Cl]_o is the concentration of Cl^- in the extracellular fluid. Note that the extracellular and intracellular concentration units must match.
• [Cl]_i is the concentration of Cl^- in the intracellular fluid. Note that the extracellular and intracellular concentration units must match.

• Universal Gas Constant (R) = 8.314 J.K^-1.mol^-1
• Faraday's Constant (F) = 96485 C.mol^-1
• Valence of Na⁺ (z_Na) = +1.
• Valence of Cl^- (z_Cl) = -1.

Enter appropriate values in all cells except the one you wish to calculate. Therefore, at least seven cells must have values, and no more than one cell may be blank. The value of the blank cell will be calculated based on the other values entered. The calculated equilibrium potentials for Na⁺ (V_Na) and Cl^- (V_Cl) are read-only values.

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