TY - JOUR

T1 - Excitation wave propagation as a possible mechanism for signal transmission in pancreatic islets of Langerhans

AU - Aslanidi, O V

AU - Mornev, O A

AU - Skyggebjerg, Ole

AU - Arkhammar, P

AU - Thastrup, Ole

AU - Sørensen, M P

AU - Christiansen, P L

AU - Conradsen, Knut

AU - Scott, Alwyn C.

PY - 2001

Y1 - 2001

N2 - In response to glucose application, beta-cells forming pancreatic islets of Langerhans start bursting oscillations of the membrane potential and intracellular calcium concentration, inducing insulin secretion by the cells. Until recently, it has been assumed that the bursting activity of beta-cells in a single islet of Langerhans is synchronized across the whole islet due to coupling between the cells. However, time delays of several seconds in the activity of distant cells are usually observed in the islets of Langerhans, indicating that electrical/calcium wave propagation through the islets can occur. This work presents both experimental and theoretical evidence for wave propagation in the islets of Langerhans. Experiments with Fura-2 fluorescence monitoring of spatiotemporal calcium dynamics in the islets have clearly shown such wave propagation. Furthermore, numerical simulations of the model describing a cluster of electrically coupled beta-cells have supported our view that the experimentally observed calcium waves are due to electric pulses propagating through the cluster. This point of view is also supported by independent experimental results. Based on the model equations, an approximate analytical expression for the wave velocity is introduced, indicating which parameters can alter the velocity. We point to the possible role of the observed waves as signals controlling the insulin secretion inside the islets of Langerhans, in particular, in the regions that cannot be reached by any external stimuli such as high glucose concentration outside the islets.

AB - In response to glucose application, beta-cells forming pancreatic islets of Langerhans start bursting oscillations of the membrane potential and intracellular calcium concentration, inducing insulin secretion by the cells. Until recently, it has been assumed that the bursting activity of beta-cells in a single islet of Langerhans is synchronized across the whole islet due to coupling between the cells. However, time delays of several seconds in the activity of distant cells are usually observed in the islets of Langerhans, indicating that electrical/calcium wave propagation through the islets can occur. This work presents both experimental and theoretical evidence for wave propagation in the islets of Langerhans. Experiments with Fura-2 fluorescence monitoring of spatiotemporal calcium dynamics in the islets have clearly shown such wave propagation. Furthermore, numerical simulations of the model describing a cluster of electrically coupled beta-cells have supported our view that the experimentally observed calcium waves are due to electric pulses propagating through the cluster. This point of view is also supported by independent experimental results. Based on the model equations, an approximate analytical expression for the wave velocity is introduced, indicating which parameters can alter the velocity. We point to the possible role of the observed waves as signals controlling the insulin secretion inside the islets of Langerhans, in particular, in the regions that cannot be reached by any external stimuli such as high glucose concentration outside the islets.

KW - Animals

KW - Calcium

KW - Calcium Signaling

KW - Islets of Langerhans

KW - Kinetics

KW - Mathematics

KW - Mice

KW - Mice, Inbred Strains

KW - Microscopy, Fluorescence

KW - Models, Biological

U2 - 10.1016/S0006-3495(01)76096-1

DO - 10.1016/S0006-3495(01)76096-1

M3 - Journal article

C2 - 11222284

VL - 80

SP - 1195

EP - 1209

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 3

ER -