We use cookies to ensure that we give you the best experience on our website. You can change your cookie settings at any time. Otherwise, we'll assume you're OK to continue.

Durham University

Research & business

View Profile

Publication details for Dr Robert William Banks

Simon, A., Banks, R. W. & Bewick, G. S. (2009), KCa channels regulate stretch-evoked afferent firing from muscle spindles, Proceedings of the Physiological Society 15: Dublin, Physiological Society, 28P.

Author(s) from Durham


Muscle spindles constantly report skeletal muscle length and movement. Mechanosensory transduction occurs at annulospiral terminals around intrafusal muscle fibres. We reported that Ca2+-dependent glutamate release from synaptic-like vesicles in these terminals modulates spindle firing (Bewick et al., 2005). To test if voltage-gated Ca2+ channels (VGCCs) or Ca2+-dependent K+ channels (KCa) are also functionally important, we tested whether channel-selective neurotoxins affected spindle afferent discharge. Adult Sprague-Dawley rats (male, 300-370 g) were killed (Schedule 1, Animal (Scientific Procedures) Act, 1986) and 4th lumbrical nerve-muscle preparations excised and placed in gassed (95%O2-5%CO2) Liley`s saline. Spindle afferent discharges were recorded en passant with Ag wire electrodes and firing frequency (mean ± SE, n) determined for the first 0.5 s of the “hold” phase of stretch-and-hold cycles (~10% muscle length) for ‘n’ preparations. The significance of differences between pre-drug and with-drug means was evaluated by paired t-test, with a threshold of P < 0.05. Unlike inorganic Ca2+ channel blockers Co2+ and Ni2+/Cd2+, which abolish responses (Bewick et al., 2005), P/Q type VGCC inhibitors enhanced firing. ω-Agatoxin-IVA (200 nM, P/Q type) increased firing to 301% of control (92.7 ± 15.8 imp/s vs 278.6 ± 23.9 imp/s, 6; P < 0.0001). ω-Conotoxin-MVIIC (1 μM, Q type) enhanced firing to 202% (98.40 ± 21.83 imp/s vs 199.60 ± 24.62 imp/s, 5; P < 0.002). Conversely, ω-conotoxin-GVIA (1 μM; N type) had no significant effect (176.92 ± 14.77 imp/s vs 196.92 ± 10.47 imp/s, 6; P = 0.1). L-type blockers Taicatoxin (50 nM, 4) and Nifedipine (10 μM, 5) increased afferent firing (131.88 ± 10.05 imp/s vs 302.13 ± 25.17 imp/s and 192.00 ± 13.09 imp/s vs 271.70 ± 9.56 imp/s, respectively) but also caused spontaneous muscle twitching, suggesting actions on skeletal muscle dihydropyridine receptors. Thus, only P/Q type channel blockers increased afferent discharge in the absence of other effects. P/Q type channels often regulate KCa (BK or SK) channel opening (Edgerton & Reinhart, 2003). Therefore, selective KCa channel blockers were applied. Charybdotoxin (200 nM; SK & BK), iberiotoxin (200 nM; BK selective) and apamin (200 nM; SK selective) all increased afferent discharge (to 195%, 4; 224%, 4 & 160%, 6 of control, respectively; all P < 0.02). Conversely, NS1619 (BK channel activator) inhibited firing (1 μM, 179.75 ± 14.35 imp/s vs 33.25 ± 18.44 imp/s, 6). This was not due to voltage-gated potassium channel or action potential conduction block, since NS1619 did not affect Nervus saphenus compound action potential amplitude (100 μM, 4). The data suggest Ca2+ entry through P/Q type channels activates KCa channels to regulate firing frequency in spindle 1a afferents.