Inhibitory effects of scorpion venom heat resistant protein on the excitability of acutely isolated rat hippocampal neurons / 生理学报

ABSTRACT

The effects of scorpion venom heat resistant protein (SVHRP) (National invention patent of China, 2004-10-20, No. ZL01 1 06166.92) on the excitability of acutely isolated rat hippocampal neurons were observed by whole-cell recording and the potential molecular mechanisms underlying its antiepileptic effect were investigated further. The results showed that SVHRP could decrease the excitability of hippocampal neurons. SVHRP (1x 10(-2) microg/mL) altered the action potential (AP) firing mode and decreased the AP firing frequency. Out of 52 neurons observed, 45 (86.54%) generated phasic firing, and 7 (13.46%) generated repetitive firing. Among the 45 neurons generating phasic firing, 8 (17.78%) neurons could still be induced phasic firing after treatment with 1x 10(-2) microg/mL SVHRP and 37 (82.22%) neurons had no responses to the stimulation. The AP firing of neurons was dramatically different after treatment with SVHRP (P<0.01, n=45). Among the 7 repetitive firing neurons, all of them could only generate 1 or 0 AP instead of repetitive firing when SVHRP was applied. The number of APs was 14.57 +/- 1.00 and 0.57 +/- 0.20 before and after SVHRP treatment (P<0.01, n=7). The AP rheobase was (75.10 +/- 8.99) pA and (119.85 +/- 12.73) pA before and after 1x 10(-4) microg/mL SVHRP application, respectively (P<0.01, n=8). The AP threshold was increased from (-41.17 +/- 2.15) mV to (-32.40 +/- 1.48) mV after 1x 10(-4) microg/mL SVHRP treatment (P<0.01, n=8). The peak amplitude of AP was (68.49 +/- 2.33) mV for the neurons before treatment with 1x 10(-4) microg/mL SVHRP and (54.71 +/- 0.81) mV after treatment (P<0.01, n=8). These results showed that SVHRP could decrease the AP firing frequency, increase the AP rheobase and threshold, but decrease the AP peak amplitude of hippocampal neurons. In other words, SVHRP can decrease the excitability of hippocampal neurons. SVHRP probably alters the excitability of hippocampal neurons by affecting sodium channels and this may be one of the underlying molecular mechanisms for its antiepileptic effect.