A voltage-activated proton current in human cardiac fibroblasts, measured using the whole-cell recording configuration of the patch-clamp technique. is reported. Increasing the pH of the bathing solution shifted the Current activation threshold to more negative potentials and increased both the current amplitude and its rate of activation. Changing the pII gradient by one unit caused a 51 mV shift in the reversal potential of the current, demonstrating a high selectivity for protons of the channel carrying, the current. Extracellularly applied Zn2+ reversibly inhibited the current. Activation of the current contributes to the testing membrane conductance under conditions of intracellular acidosis. It is proposed that this current in cardiac fibroblasts is invoked in the regulation of the intracellular pH and the membrane potential under physiological conditions as well as in response to pathological conditions Such as ischemia. (c) 2005 Elsevier Inc. All rights reserved.