Reduced Potassium Currents in Old Rat CA1 Hippocampal Neurons W.B. Alshuaib, 1 * S.M. Hasan, 1 S.P. Cherian, 1 M.V. Mathew, 1 M.Y. Hasan, 2 and M.A. Fahim 2 1 Department of Physiology, Faculty of Medicine, Kuwait University, Kuwait 2 Departments of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates Potassium currents are an important factor in repolariz- ing the membrane potential and determining the level of neuronal excitability. We compared potassium currents in CA1 hippocampal neurons dissociated from young (2–3 months old) and old (26 –30 months old) Sprague– Dawley rats. Whole-cell patch-clamp techniques were used to measure the delayed rectifier (sustained) and the A-type (transient) potassium currents. The delayed rec- tifier current was smaller in old (548  57 pA) than in young (1193  171 pA) neurons. In the absence of ex- tracellular calcium, the delayed rectifier current was also smaller in old (427  41 pA) than in young (946  144 pA) neurons. The cell membrane capacitance was un- changed in old (13.3  1.2 pF) compared to young (13.6  1.2 pF). Therefore, the reduction in the delayed rectifier current was not due to a change in membrane surface area. Moreover, activation and inactivation of the delayed rectifier current were unchanged in old com- pared to young neurons. The slope of the current-voltage relation, however, was smaller in old (B = 5.03) than in young (B = 9.62) neurons. Similarly, the A-current was smaller in old (100  16 pA) than in young (210  44 pA) neurons in the presence of extracellular calcium. This reduction of potassium currents could account for the prolongation of action potentials reported previously for old rat CA1 hippocampal neurons. The age-related re- duction in potassium current indicates plasticity in neu- ronal function that can impact communication in the hippocampal neural network during aging. J. Neurosci. Res. 63:176 –184, 2001. © 2001 Wiley-Liss, Inc. Key words: aging; hippocampus; delayed rectifier; A- current; calcium The delayed rectifier (IK DR ) and the A-type (IK A ) potassium currents are voltage-dependent and they play a major role in regulating neuronal excitability (Hablitz and Johnson, 1981; Wong and Traub, 1983; Klee et al., 1995). Changes in the number of delayed rectifier and A-type channels or changes in their kinetic properties can alter neuronal electrical function (LeMasson et al., 1993). IK DR contributes to the action potential repolarization, whereas IK A regulates the membrane potential between action potentials. Previous studies of the rat hippocampus have not shown any change in potassium currents measured from cultured young and old neurons (Evans et al., 1998). An age-related increase of after-hyperpolarization (AHP) in CA1 pyramidal neurons has been reported for Fisher rats (Landfield and Pitler, 1984; Kerr et al., 1989) and rabbits (Moyer et al., 1992; Disterhoft et al., 1996). By contrast, other studies have reported no change in AHP in the CA1 region of Fisher and Sprague–Dawley rats (Potier et al., 1992). The calcium-dependent potassium current (IK Ca ) underlies AHP. It has been suggested that calcium ho- meostasis is modified in hippocampal neurons in the old rat. An increase in the duration of action potentials has been reported for old rat hippocampal neurons (Landfield and Pitler, 1984; Pitler and Landfield, 1990; Disterhoft et al., 1993; Campbell et al., 1996). There are no major age-related changes in the passive membrane properties of CA1 hippocampal neurons, namely the resting membrane potential (RMP) and input resistance (Rin) (Moyer and Disterhoft, 1994; Campbell et al., 1996). A larger depo- larizing current was required in old than in young CA1 neurons to produce an action potential (Turner and Deu- pree, 1991; Potier et al., 1992). The number of neurons in the CA1 hippocampal region has been reported to be similar in young and old rats (Barnes and McNaughton, 1980). Ultrastructural stud- ies, however, have demonstrated that the number of syn- apses are depleted in the old rat hippocampus (Geinisman et al., 1992). Within the hippocampus, by far the most commonly studied pathway is the Schaffer collateral input to pyramidal neurons of the CA1 region (Zigmond et al., 1999). The size of the excitatory postsynaptic potential (EPSP) field is decreased with aging (Barnes et al., 1992; Deupree et al., 1993). This implies a reduction in the number of functional synaptic contacts made by individual Contract grant sponsor: Kuwait University; Contract grant number: MPY 032. *Correspondence to: Dr. Waleed B. Alshuaib, Department of Physiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. E-mail: Waleed@hsc.Kuniv.edu.Kw Received 30 June 2000; Revised 12 September 2000; Accepted 29 Sep- tember 2000 Journal of Neuroscience Research 63:176 –184 (2001) © 2001 Wiley-Liss, Inc.