Effect of temperature on limitation by MK-801 of firing of action potentials by spinal cord neurons in cell culture

Abstract

The anticonvulsant, MK-801, limited sustained high frequency repetitive firing of sodium-dependent action potentials by mouse spinal cord neurons in monolayer dissociated cell culture. Limitation was voltage- and temperature-dependent and was accompanied by decreasing rate of rise of action potentials until firing ceased during the 400 ms depolarizations. The IC 50 for limitation was 2 × 10 −7 M at 37°C, 6.4 × 10 −7 M at 35°C, and 4 × 10 −5 M at 23°C. The relationship between the percentage of neurons capable of sustained repetitive firing and MK-801 concentration at 33°C was biphasic. The first phase (about 50%) of limitation had IC 50a = 1.5 × 10 −7 M, and the second had IC 50b = 2 × 10 −4 M; the midpoint of the connecting plateau was 10 −5 M. At temperatures below 37°C, the current needed to achieve maximal firing increased. The maximal rate of rise, maximal firing frequency and sensitivity to MK-801 of action potentials elicited by 1 ms stimuli decreased at temperatures below 37°C. Passive membrane properties were unchanged. Slow firing and a temperature-sensitive conformational change in voltage-activated sodium channels could account for the higher concentrations of MK-801 required to block sodium-dependent action potentials at temperatures below 37°C.