In low or absence of glucose, alpha-cells generate rhythmic action potentials and secrete glucagon. alpha-Cell T-type Ca2+ channels are believed to be pacemaker channels, which are expected to open near the resting membrane potential (around -60 mV) to initiate a small depolarization. A previous publication, however, showed that alpha-cell T-type Ca2+ channels have an activation threshold of -40 mV, which does not appear to fulfill their role as pacemakers. In this work, we investigated the Ca2+ channel characteristics in alpha-cells of mouse-insulin-promoter green-fluoreseent-protein (MIP-GFP) mouse. The beta-cells of MIP-GFP were conveniently distinguished as green cells, while immunostaining indicated that the majority of non-green cells were alpha-cells. We found that majority of alpha-cells possessed T-type Ca2+ channels having an activation threshold of -40 mV; these cells also had high-voltage-activated (HVA) Ca2+ channels (activation threshold of -20 mV). A novel finding here is that a minority of Cc-cells had T-type Ca2+ channels with an activation threshold of -60 mV. This minor population of alpha-cells was, surprisingly, devoid of HVA Ca2+ channels. We suggest that this alpha-cell subpopulation may act as pacemaker cells in low or absence of glucose. (c) 2006 Elsevier Inc. All rights reserved.