Figure 4.
Voltage-gated ion channels are critical for thermal block, and voltage-dependent potassium channels dominate the block at higher temperatures. (A) and (K) Schematic of the experiment. The central region of a model axon was changed to a temperature, , that blocked action potential propagation for the original Hodgkin/Huxley model (A) and for the modified model (K). Regions of the axon before and after the central region were kept at the control temperature of 6.3 °C. An action potential was initiated at the left-hand side of the model axon with a current of 2000 nA (1 ms duration), and the propagating action potential was measured as it reached the region of changed temperature (point labeled 1) and at the end of the axon (point labeled 2). (B), (C), (L) and (M) Control responses. When the central region remained at 6.3 °C, the action potential propagated normally through the region and reached the end of the axon ((B), (C), (L) and (M), solid blue lines). As the action potential reached the central region subjected to a higher temperature, it was reduced in amplitude ((B) and (L), dashed red lines; compare to solid blue lines), and it was completely blocked at the end of the axon ((C) and (M), dashed red lines). (D), (E), (N) and (O) The conductances of both the voltage-gated sodium ion and potassium ion channels were set to zero in the central region. When the temperature of the central region was not changed, the action potential shape changed slightly as it reached the region without ion channels ((D) and (N), solid blue lines), but by the end of the axon, its shape was again similar to the control action potential ((E) and (O), solid blue lines). When the central region is subjected to an increase in temperature, there is no change in the action potential in the Hodgkin/Huxley model ((D) and (E); the dashed red lines are completely covered by the solid blue lines). A slight widening of the action potential is visible in the modified Hodgkin/Huxley model as the action potential reaches the region at a higher temperature ((N), dashed red line), but the action potential at the end of the axon is identical to that generated when the central region is at its original temperature ((O); dashed red line is covered by solid blue line). (F), (G), (P) and (Q) Voltage-dependent potassium channels are sufficient to induce thermal block. The conductance of the voltage-dependent sodium ion channels was set to zero in the central region. The peaks of the action potentials were slightly reduced when the central region was at its original temperature ((F) and (P), solid blue lines), but the action potentials at the end of the axon were similar to control action potentials ((G) and (Q), solid blue lines). In contrast, increasing the temperature of the central region blocked action potentials. The action potential was reduced as it reached the region of increased temperature ((F) and (P), dashed red lines), and was completely absent at the end of the axon ((G) and (Q), dashed red lines). (H), (I), (R) and (S) Voltage-dependent potassium channels are necessary to induce thermal block. The conductance of the voltage-dependent potassium ion channels was set to zero in the central region. As the action potentials reached the central region, they were slightly wider than normal ((H) and (R), solid blue lines), but were similar to control action potentials at the end of the axon ((I) and (S), solid blue lines). Action potentials were not blocked by increased temperature; they narrowed as they reached the region of increased temperature ((H) and (R), dashed red lines), but were essentially similar to control action potentials at the end of the axon ((I) and (S), dashed red lines; in (S), the solid blue line covers the dashed red line). (J) and (T) Minimum lengths required to block the action potential when all voltage-gated ion channels are intact (dashed red line) are similar to those needed to block when only voltage-gated potassium ion channels are present (light red line), especially at higher temperatures. At low temperatures, the original Hodgkin/Huxley model is also affected by the effects of temperature on the voltage-gated sodium ion channels. At high temperatures, the voltage-gated potassium ion channels clearly dominate the block length (J), and these channels dominate at all temperatures in the modified model (T). The dashed vertical lines in (J) and (T) (at 35 °C and 29.5 °C, respectively), correspond to the results shown in parts (A)–(I) and (K)–(S) of this figure, respectively.