Identification of CaV channel types expressed in muscle afferent neurons

Renuka Ramachandra, Bassil Hassan, Stephanie G. McGrew, James Dompor, Mohamed Farrag, Victor Ruiz-Velasco, Keith S. Elmslie

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Cardiovascular adjustments to exercise are partially mediated by group III/IV (small to medium) muscle afferents comprising the exercise pressor reflex (EPR). However, this reflex can be inappropriately activated in disease states (e.g., peripheral vascular disease), leading to increased risk of myocardial infarction. Here we investigate the voltage-dependent calcium (CaV) channels expressed in small to medium muscle afferent neurons as a first step toward determining their potential role in controlling the EPR. Using specific blockers and 5 mM Ba2+ as the charge carrier, we found the major calcium channel types to be CaV2.2 (N-type) > CaV2.1 (P/Q-type) > CaV1.2 (L-type). Surprisingly, the CaV2.3 channel (R-type) blocker SNX482 was without effect. However, R-type currents are more prominent when recorded in Ca2+ (Liang and Elmslie 2001). We reexamined the channel types using 10 mM Ca2+ as the charge carrier, but results were similar to those in Ba2+. SNX482 was without effect even though ~27% of the current was blocker insensitive. Using multiple methods, we demonstrate that CaV2.3 channels are functionally expressed in muscle afferent neurons. Finally, ATP is an important modulator of the EPR, and we examined the effect on CaV currents. ATP reduced CaV current primarily via G protein βγ-mediated inhibition of CaV2.2 channels. We conclude that small to medium muscle afferent neurons primarily express CaV2.2 > CaV2.1 ≥ CaV2.3 > CaV1.2 channels. As with chronic pain, CaV2.2 channel blockers may be useful in controlling inappropriate activation of the EPR.

Original languageEnglish (US)
Pages (from-to)1535-1543
Number of pages9
JournalJournal of neurophysiology
Volume110
Issue number7
DOIs
StatePublished - Oct 1 2013

Fingerprint

Afferent Neurons
Reflex
Muscles
Calcium Channels
Adenosine Triphosphate
Social Adjustment
Peripheral Vascular Diseases
GTP-Binding Proteins
Chronic Pain
Myocardial Infarction

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

Cite this

Ramachandra, R., Hassan, B., McGrew, S. G., Dompor, J., Farrag, M., Ruiz-Velasco, V., & Elmslie, K. S. (2013). Identification of CaV channel types expressed in muscle afferent neurons. Journal of neurophysiology, 110(7), 1535-1543. https://doi.org/10.1152/jn.00069.2013
Ramachandra, Renuka ; Hassan, Bassil ; McGrew, Stephanie G. ; Dompor, James ; Farrag, Mohamed ; Ruiz-Velasco, Victor ; Elmslie, Keith S. / Identification of CaV channel types expressed in muscle afferent neurons. In: Journal of neurophysiology. 2013 ; Vol. 110, No. 7. pp. 1535-1543.
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Ramachandra, R, Hassan, B, McGrew, SG, Dompor, J, Farrag, M, Ruiz-Velasco, V & Elmslie, KS 2013, 'Identification of CaV channel types expressed in muscle afferent neurons', Journal of neurophysiology, vol. 110, no. 7, pp. 1535-1543. https://doi.org/10.1152/jn.00069.2013

Identification of CaV channel types expressed in muscle afferent neurons. / Ramachandra, Renuka; Hassan, Bassil; McGrew, Stephanie G.; Dompor, James; Farrag, Mohamed; Ruiz-Velasco, Victor; Elmslie, Keith S.

In: Journal of neurophysiology, Vol. 110, No. 7, 01.10.2013, p. 1535-1543.

Research output: Contribution to journalArticle

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T1 - Identification of CaV channel types expressed in muscle afferent neurons

AU - Ramachandra, Renuka

AU - Hassan, Bassil

AU - McGrew, Stephanie G.

AU - Dompor, James

AU - Farrag, Mohamed

AU - Ruiz-Velasco, Victor

AU - Elmslie, Keith S.

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N2 - Cardiovascular adjustments to exercise are partially mediated by group III/IV (small to medium) muscle afferents comprising the exercise pressor reflex (EPR). However, this reflex can be inappropriately activated in disease states (e.g., peripheral vascular disease), leading to increased risk of myocardial infarction. Here we investigate the voltage-dependent calcium (CaV) channels expressed in small to medium muscle afferent neurons as a first step toward determining their potential role in controlling the EPR. Using specific blockers and 5 mM Ba2+ as the charge carrier, we found the major calcium channel types to be CaV2.2 (N-type) > CaV2.1 (P/Q-type) > CaV1.2 (L-type). Surprisingly, the CaV2.3 channel (R-type) blocker SNX482 was without effect. However, R-type currents are more prominent when recorded in Ca2+ (Liang and Elmslie 2001). We reexamined the channel types using 10 mM Ca2+ as the charge carrier, but results were similar to those in Ba2+. SNX482 was without effect even though ~27% of the current was blocker insensitive. Using multiple methods, we demonstrate that CaV2.3 channels are functionally expressed in muscle afferent neurons. Finally, ATP is an important modulator of the EPR, and we examined the effect on CaV currents. ATP reduced CaV current primarily via G protein βγ-mediated inhibition of CaV2.2 channels. We conclude that small to medium muscle afferent neurons primarily express CaV2.2 > CaV2.1 ≥ CaV2.3 > CaV1.2 channels. As with chronic pain, CaV2.2 channel blockers may be useful in controlling inappropriate activation of the EPR.

AB - Cardiovascular adjustments to exercise are partially mediated by group III/IV (small to medium) muscle afferents comprising the exercise pressor reflex (EPR). However, this reflex can be inappropriately activated in disease states (e.g., peripheral vascular disease), leading to increased risk of myocardial infarction. Here we investigate the voltage-dependent calcium (CaV) channels expressed in small to medium muscle afferent neurons as a first step toward determining their potential role in controlling the EPR. Using specific blockers and 5 mM Ba2+ as the charge carrier, we found the major calcium channel types to be CaV2.2 (N-type) > CaV2.1 (P/Q-type) > CaV1.2 (L-type). Surprisingly, the CaV2.3 channel (R-type) blocker SNX482 was without effect. However, R-type currents are more prominent when recorded in Ca2+ (Liang and Elmslie 2001). We reexamined the channel types using 10 mM Ca2+ as the charge carrier, but results were similar to those in Ba2+. SNX482 was without effect even though ~27% of the current was blocker insensitive. Using multiple methods, we demonstrate that CaV2.3 channels are functionally expressed in muscle afferent neurons. Finally, ATP is an important modulator of the EPR, and we examined the effect on CaV currents. ATP reduced CaV current primarily via G protein βγ-mediated inhibition of CaV2.2 channels. We conclude that small to medium muscle afferent neurons primarily express CaV2.2 > CaV2.1 ≥ CaV2.3 > CaV1.2 channels. As with chronic pain, CaV2.2 channel blockers may be useful in controlling inappropriate activation of the EPR.

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